bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of diode laser and subgingival air polishing with erythritol in treatment of periodontitis (clinical and microbiological study)
Authors: Elmeligy Sara M. A. , Saleh Wafaa , Elewa Gasser M. , Abu El-Ezz Hani Z , Mahmoud Noha Mostafa , Elmeadawy Samah
Published: July 2024

Background

There is insufficient clinical and microbiological evidence to support the use of diode laser and air-polishing with erythritol as supplements to scaling and root planning(SRP). The aim of the current study is to evaluate the clinical and microbiologic efficacy of erythritol subgingival air polishing and diode laser in treatment of periodontitis.

Methods

The study encompassed twenty-four individuals seeking periodontal therapy and diagnosed with stage I and stage II periodontitis. Eight patients simply underwent SRP. Eight more patients had SRP followed by erythritol subgingival air polishing, and eight patients had SRP followed by diode laser application. At baseline and six weeks, clinical periodontal parameters were measured, including Plaque Index (PI), Gingival Index (GI), periodontal Probing Depth (PPD), and Clinical Attachment Level (CAL). The bacterial count of Aggregatibacter actinomycetemcomitans(A.A), Porphyromonas gingivalis (P.G) was evaluated at different points of time.

Results

The microbiological assessment revealed significant differences in the count of A.A. between the laser and erythritol groups immediately after treatment, indicating a potential impact on microbial levels. However, the microbial levels showed fluctuations over the subsequent weeks, without statistically significant differences. Plaque indices significantly decreased post-treatment in all groups, with no significant inter-group differences. Gingival indices decreased, and the laser group showed lower values than erythritol and control groups. PPD and CAL decreased significantly across all groups, with the laser group exhibiting the lowest values.

Conclusion

The supplementary use of diode laser and erythritol air polishing, alongside SRP, represents an expedited periodontal treatment modality. This approach leads to a reduction in bacteria and improvement in periodontal health.

Trial registration

This clinical trial was registered on Clinical Trials.gov (Registration ID: NCT06209554) and released on 08/01/2024.
Bidirectional causality between the levels of blood lipids and endometriosis: a two-sample mendelian randomization study
Authors: Wang Zhenna , Zhan Chunxian , Liao Linghua , Luo Ye , Lin Shunhe , Yan Shihan
Published: July 2024

Background

Observational studies have found a correlation between the levels of blood lipids and the development and progression of endometriosis (EM). However, the causality and direction of this correlation is unclear. This study aimed to examine the bidirectional connection between lipid profiles and the risk of EM using publicly available genome-wide association study (GWAS) summary statistics.

Methods

Eligible exposure variables such as levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were selected using a two-sample Mendelian randomization (MR) analysis method following a series of quality control procedures. Data on EM were obtained from the publicly available Finnish database of European patients. Inverse variance weighted (IVW), MR Egger, weighted median, and weighted mode methods were used to analyze the causal relationship between lipid exposure and EM, exclude confounders, perform sensitivity analyses, and assess the stability of the results. Reverse MR analyses were performed with EM as exposure and lipid results as study outcomes.

Results

IVW analysis results identified HDL as a protective factor for EM, while TG was shown to be a risk factor for EM. Subgroup analyses based on the site of the EM lesion identified HDL as a protective factor for EM of the uterus, while TG was identified a risk factor for the EM of the fallopian tube, ovary, and pelvic peritoneum. Reverse analysis did not reveal any effect of EM on the levels of lipids.

Conclusion

Blood lipids, such as HDL and TG, may play an important role in the development and progression of EM. However, EM does not lead to dyslipidemia.
DNA methylation of exercise-responsive genes differs between trained and untrained men
Authors: Geiger Carla , Needhamsen Maria , Emanuelsson Eric B. , Norrbom Jessica , Steindorf Karen , Sundberg Carl Johan , Reitzner Stefan M. , Lindholm Malene E.
Published: July 2024

Background

Physical activity is well known for its multiple health benefits and although the knowledge of the underlying molecular mechanisms is increasing, our understanding of the role of epigenetics in long-term training adaptation remains incomplete. In this intervention study, we included individuals with a history of > 15 years of regular endurance or resistance training compared to age-matched untrained controls performing endurance or resistance exercise. We examined skeletal muscle DNA methylation of genes involved in key adaptation processes, including myogenesis, gene regulation, angiogenesis and metabolism.

Results

A greater number of differentially methylated regions and differentially expressed genes were identified when comparing the endurance group with the control group than in the comparison between the strength group and the control group at baseline. Although the cellular composition of skeletal muscle samples was generally consistent across groups, variations were observed in the distribution of muscle fiber types. Slow-twitch fiber type genes MYH7 and MYL3 exhibited lower promoter methylation and elevated expression in endurance-trained athletes, while the same group showed higher methylation in transcription factors such as FOXO3, CREB5, and PGC-1α. The baseline DNA methylation state of those genes was associated with the transcriptional response to an acute bout of exercise. Acute exercise altered very few of the investigated CpG sites.

Conclusions

Endurance- compared to resistance-trained athletes and untrained individuals demonstrated a different DNA methylation signature of selected skeletal muscle genes, which may influence transcriptional dynamics following a bout of acute exercise. Skeletal muscle fiber type distribution is associated with methylation of fiber type specific genes. Our results suggest that the baseline DNA methylation landscape in skeletal muscle influences the transcription of regulatory genes in response to an acute exercise bout.
Retraction Note: DNA barcoding detects contamination and substitution in North American herbal products
Authors:   BMC Medicine Editorial Office
Published: July 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1741-7015-11-222.
Overview on the role of dietary Spirulina platensis on immune responses against Edwardsiellosis among Oreochromis niloticus fish farms
Authors: Okasha Lamiaa A. , Abdellatif Jehan I. , Abd-Elmegeed Ola H. , Sherif Ahmed H.
Published: July 2024

Edwardsiellosis is a bacterial fish disease that mostly occurs in freshwater farms and is characterized by a high mortality rate. Edwardsiella tarda strain was recovered from 17 fish out of 50 Nile tilapia, which were harboring clinical signs of systemic septicemia. The level of un-ionized ammonia (NH3) in the fish farm’s water was 0.11–0.15 mg/L, which was stressful for the Nile tilapia.

Sequencing of the gyrB1 gene confirmed that the isolate was E. tarda JALO4, and it was submitted to NCBI under the accession number PP449014. The isolated E. tarda harbored the virulence gene edw1 AHL-synthase (quorum sensing). In addition, the isolate was sensitive to trimethoprim and sulfamethoxazole mean while it was intermediate to florfenicol. The median lethal dose (LD50) of E. tarda JALO4 was determined to be 1.7 × 105 CFU/mL in Nile tilapia.

In the indoor experiment, Nile tilapia (45.05 ± 0.4 g), which received dietary Spirulina platensis (5 and 10 g/kg fish feed), showed optimum growth and feed utilization. Meanwhile, after receiving dietary S. platensis, the fish’s feed conversion ratio (FCR) was significantly enhanced compared to the control, which was 1.94, 1.99, and 2.88, respectively. The expression of immune-related genes interleukin (IL)-1β and tumor necrosis factor (TNF)-α were upsurged in E. tarda-challenged fish with higher intensity in S. platensis groups. Dietary S. platensis at a dose of 10 g/kg fish feed could provide a relative protection level (RPL) of 22.2% Nile tilapia challenged against E. tarda. Nile tilapia experimentally infected E. tarda, drastically altering their behavior: higher operculum movement, low food apprehension, and abnormal swimming dietary S. platensis (10 g/kg fish feed) could rapidly restore normal status.

It was concluded that Edwardsiellosis could alter Nile tilapia behavior with a high loss in fish population. Fish received dietary-S. platensis could rapidly restore normal behavior after E. tarda infection. It is recommended the incorporation of S. platensis at doses of 10 g/kg into the Nile tilapia diet to boost their immunity and counteract E. tarda infection.
The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia
Authors: Wei DiWei , Zhao YiDi , Zhang TongQiang , Xu YongSheng , Guo Wei
Published: July 2024

Background

This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission.

Methods

We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children’s Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2–10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman’s rank correlation coefficient was used to assess relationships between variables.

Results

The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001).

Conclusions

Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.
Successes and challenges of partnership working to tackle health inequalities using collaborative approaches to community-based research: mixed methods analysis of focus group evidence
Authors: Thomson L. J. M. , Waterson H. , Chatterjee H. J.
Published: July 2024

Background

The concept of collaborative approaches involves community residents in joint decision-making processes to maintain or enhance their material and social conditions. During COVID-19, public services saw the benefits of actively collaborating with communities and involving residents in decision-making processes. As communities have resources and assets, they are well-placed to contribute to developing local health and wellbeing initiatives. An interdisciplinary and nationally funded three-phase research programme, “Mobilising community assets to tackle health inequalities”, was established with the objective of utilising local, cultural, and natural assets to support health and wellbeing. The current study aimed to synthesise evidence collected by research teams awarded funding in phase one of the programme, comprising academic and non-academic, health and social care, voluntary and community partners.

Methods

Ten online focus groups were conducted with research teams from across the UK exploring the successes and challenges of partnership working to tackle health inequalities using collaborative approaches to community-based research. Eight focus group questions were split between partnership working and health inequalities.

Results

Thematic and content analysis produced 185 subthemes from which 12 themes were identified. Major themes representing an above average number of coded responses were research evidence; funding; relationships with partners; health inequalities and deprivation; community involvement; and health service and integrated care systems. Minor themes were link workers and social prescribing; training and support; place-based factors; longevity of programmes; setting up and scaling up programmes; and mental health.

Conclusions

Successes included employing practice-based and arts-based methods, being part of a research project for those not normally involved in research, sharing funding democratically, building on established relationships, and the vital role that local assets play in involving communities. Challenges involved a lack of sustainable financial support, the short-term nature of funding, inconsistencies in reaching the poorest people, obtaining the right sort of research evidence, making sufficient research progress, building relationships with already over-burdened health care staff, and redressing the balance of power in favour of communities. Despite the challenges, participants were mainly optimistic that collective approaches and meaningful co-production would create opportunities for future research partnerships with communities.
Non-O blood types are associated with a greater risk of large artery atherosclerosis stroke and dysregulation of cholesterol metabolism: an observational study
Authors: Gou Lan , Li Haowen , Jiang Yingyu , Liu Yang , Gu Hongqiu , Xu Zhe , Jin Weina , Li Lanxin , Shi Yanfeng , Zhang Jie , Fang Zhenjuan , Meng Xia , Jiang Yong , Li Hao , Wang Yongjun , Cheng Si
Published: July 2024

Background

Previous research on ABO blood types and stroke has been controversial, predominantly suggesting heightened risk of stroke in non-O blood types. Nonetheless, investigations into the correlation and underlying mechanisms between ABO blood groups and stroke subtypes, especially within Chinese cohorts, remain limited.

Methods

The ABO blood types of 9,542 ischaemic stroke (IS) patients were inferred using two ABO gene loci (c.261G > del; c.802G > A). The healthy population was derived from the 1000 Genomes Project. Patients were classified by the causative classification system (CCS). Volcano plot and gene ontology (GO) analysis were employed to explore protein differential expression among blood types. Additionally, HT29 and SW480 cell lines with downregulated ABO expression were generated to evaluate its impact on cholesterol uptake and efflux.

Results

A greater proportion of stroke patients had non-O blood types (70.46%) than did healthy individuals (61.54%). Notable differences in blood type distributions were observed among stroke subtypes, with non-O blood type patients mainly classified as having large artery atherosclerosis (LAA). Clinical baseline characteristics, such as the low-density lipoprotein cholesterol level, activated partial thromboplastin time and thrombin time, varied significantly among blood types. A volcano plot revealed 17 upregulated and 42 downregulated proteins in the O blood type. GO term analysis indicated that downregulated proteins were primarily associated with lipid metabolism pathways. In vitro experiments revealed that reducing ABO gene expression decreased cholesterol uptake and increased cholesterol efflux.

Conclusions

This study revealed that the non-O blood type increased the risk of LAA stroke through cholesterol metabolism.
A quantitative comparison between the essential medicines for rheumatic diseases in children and young people in Africa and the WHO model list
Authors: Slamang Waheba , Scott Christiaan , Foster Helen E.
Published: July 2024

Background

The World Health Organisation Essential Medicines List (WHO EML) guides National Essential Medicines Lists and Standard Treatment Guidelines for clearly identified disease priorities especially in low- and middle-income countries. This study compares the degree to which the basket of medicines recommended for rheumatic diseases in children and young people in National Essential Medicines Lists of countries in the WHO Africa region, corresponds to the 2021 WHO EML and WHO EML for children, as a proxy of availability.

Methods

An online search of the WHO medicines and health technology portal, the Health Ministry websites of the 54 African countries, PUBMED and Google Scholar, with search terms for ‘National Essential Medicines List’, AND/OR ‘standard treatment guidelines’ AND/OR ‘Lista Nacional de Medicamentos Essenciais’ AND/ OR ‘Liste Nationale de Medicaments Essentiels’ AND Africa AND/OR < Name of African country > was conducted. The number of medicines on the national lists were compared according to a predefined template of medicines; and the percentage similarity calculated. Descriptive statistics were derived using STATA.

Results

Forty-seven countries in the WHO Africa region have developed a National Essential Medicines List. Eleven countries do not have any medicines listed for rheumatic diseases.

The majority of countries had less than or equal to 50% similarity with the WHO EML for rheumatic disease in children and young people, median 3 medicines (IQR 1— 4). The most common medicines on the national lists from Africa were methotrexate, sulfasalazine and azathioprine, with etanercept available in 6 countries. Seven countries had only one medicine, acetylsalicylic acid listed in the section ‘Juvenile Joint diseases’.

A multiple linear regression model for the predictors of the number of medicines on the national lists established that 20% of the variability was predicted by health expenditure per capita, socio-demographic index and the availability of rheumatology services (adult and/or paediatric) p = 0.006, with socio-demographic index (p = 0.035, 95% CI 0.64—16.16) and the availability of rheumatology services (p = 0.033, 95% CI 0.13 – 2.90) significant.

Conclusion

Four countries (8.5%) in Africa have updated their National Essential Medicines Lists to reflect adequate care for children and young people with rheumatic diseases. Moving forward, efforts should focus on aligning available medicines with the WHO EML, and strengthening healthcare policy for rheumatology and pharmaceutical services, for affordable access to care and medicines.
Nucleus accumbens ghrelin signaling controls anxiety-like behavioral response to acute stress
Authors: Chang Leilei , He Yecheng , Tian Tian , Li Bin
Published: July 2024

Background

Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated.

Methods

In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests.

Results

We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects.

Conclusions

This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.
First initiation of mobilization out of bed after cardiac surgery – an observational cross-sectional study in Sweden
Authors: Westerdahl Elisabeth , Lilliecrona Johanna , Sehlin Maria , Svensson-Raskh Anna , Nygren-Bonnier Malin , Olsen Monika Fagevik
Published: July 2024

Background

Cardiac surgery is associated with a period of postoperative bed rest. Although early mobilization is a vital component of postoperative care, for preventing complications and enhancing physical recovery, there is limited data on routine practices and optimal strategies for early mobilization after cardiac surgery. The aim of the study was to define the timing for the first initiation of out of bed mobilization after cardiac surgery and to describe the type of mobilization performed.

Methods

In this observational study, the first mobilization out of bed was studied in a subset of adult cardiac surgery patients (n = 290) from five of the eight university hospitals performing cardiothoracic surgery in Sweden. Over a five-week period, patients were evaluated for mobilization routines within the initial 24 h after cardiac surgery. Data on the timing of the first mobilization after the end of surgery, as well as the duration and type of mobilization, were documented. Additionally, information on patient characteristics, anesthesia, and surgery was collected.

Results

A total of 277 patients (96%) were mobilized out of bed within the first 24 h, and 39% of these patients were mobilized within 6 h after surgery. The time to first mobilization after the end of surgery was 8.7 ± 5.5 h; median of 7.1 [4.5–13.1] hours, with no significant differences between coronary artery bypass grafting, valve surgery, aortic surgery or other procedures (p = 0.156). First mobilization session lasted 20 ± 41 min with median of 10 [1–11]. Various kinds of first-time mobilization, including sitting on the edge of the bed, standing, and sitting in a chair, were revealed. A moderate association was found between longer intubation time and later first mobilization (ρ = 0.487, p < 0.001). Additionally, there was a moderate correlation between the first timing of mobilization duration of the first mobilization session (ρ = 0.315, p < 0.001).

Conclusions

This study demonstrates a median time to first mobilization out of bed of 7 h after cardiac surgery. A moderate correlation was observed between earlier timing of mobilization and shorter duration of the mobilization session. Future research should explore reasons for delayed mobilization and investigate whether earlier mobilization correlates with clinical benefits.

Trial registration

FoU in VGR (Id 275,357) and Clinical Trials (NCT04729634).
Rhei Undulati Rhizoma attenuates memory decline and reduces amyloid-β induced neuritic dystrophy in 5xFAD mouse
Authors: Lee Seungmin , Ju In Gyoung , Eo Hyeyoon , Kim Jin Hee , Choi Yujin , Oh Myung Sook
Published: July 2024

Background

Alzheimer's disease (AD) is a common type of dementia characterized by amyloid-β (Aβ) accumulation, lysosomal dysfunction, and tau hyperphosphorylation, leading to neurite dystrophy and memory loss. This study aimed to investigate whether Rhei Undulati Rhizoma (RUR), which has been reported to have anti-neuroinflammatory effect, attenuates Aβ-induced memory impairment, neuritic dystrophy, and tau hyperphosphorylation, and to reveal its mode of action.

Methods

Five-month-old 5xFAD mice received RUR (50 mg/kg) orally for 2 months. The Y-maze test was used to assess working memory. After behavioral testing, brain tissue was analyzed using thioflavin S staining, western blotting, and immunofluorescence staining to investigate the mode of action of RUR. To confirm whether RUR directly reduces Aβ aggregation, a thioflavin T assay and dot blot were performed after incubating Aβ with RUR.

Results

RUR administration attenuated the Aβ-induced memory impairment in 5xFAD mice. Furthermore, decreased accumulation of Aβ was observed in the hippocampus of the RUR-treated 5xFAD group compare to the vehicle-treated 5xFAD group. Moreover, RUR reduced the dystrophic neurites (DNs) that accumulate impaired endolysosomal organelles around Aβ. In particular, RUR treatment downregulated the expression of β-site amyloid precursor protein cleaving enzyme 1 and the hyperphosphorylation of tau within DNs. Additionally, RUR directly suppressed the aggregation of Aβ, and eliminated Aβ oligomers in vitro.

Conclusions

This study showed that RUR could attenuate Aβ-induced pathology and directly regulate the aggregation of Aβ. These results suggest that RUR could be an efficient material for AD treatment through Aβ regulation.

Graphical Abstract
Congenital syndromic Chiari-like malformation (CSCM) in Holstein cattle: towards unravelling of possible genetic causes
Authors: Jacinto Joana Goncalves Pontes , Letko Anna , Häfliger Irene Monika , Drögemüller Cord , Agerholm Jørgen Steen
Published: July 2024

Background

Chiari malformation type II (CMII) was originally reported in humans as a rare disorder characterized by the downward herniation of the hindbrain and towering cerebellum. The congenital brain malformation is usually accompanied by spina bifida, a congenital spinal anomaly resulting from incomplete closure of the dorsal aspect of the spinal neural tube, and occasionally by other lesions. A similar disorder has been reported in several animal species, including cattle, particularly as a congenital syndrome. A cause of congenital syndromic Chiari-like malformation (CSCM) in cattle has not been reported to date. We collected a series of 14 CSCM-affected Holstein calves (13 purebred, one Red Danish Dairy F1 cross) and performed whole-genome sequencing (WGS). WGS was performed on 33 cattle, including eight cases with parents (trio-based; group 1), three cases with one parent (group 2), and three single cases (solo-based; group 3).

Results

Sequencing-based genome-wide association study of the 13 Holstein calves with CSCM and 166 controls revealed no significantly associated genome region. Assuming a single Holstein breed-specific recessive allele, no region of shared homozygosity was detected suggesting heterogeneity. Subsequent filtering for protein-changing variants that were only homozygous in the genomes of the individual cases allowed the identification of two missense variants affecting different genes, SHC4 in case 4 in group 1 and WDR45B in case 13 in group 3. Furthermore, these two variants were only observed in Holstein cattle when querying WGS data of > 5,100 animals. Alternatively, potential de novo mutational events were assessed in each case. Filtering for heterozygous private protein-changing variants identified one DYNC1H1 frameshift variant as a candidate causal dominant acting allele in case 12 in group 3. Finally, the presence of larger structural DNA variants and chromosomal abnormalities was investigated in all cases. Depth of coverage analysis revealed two different partial monosomies of chromosome 2 segments in cases 1 and 7 in group 1 and a trisomy of chromosome 12 in the WDR45B homozygous case 13 in group 3.

Conclusions

This study presents for the first time a detailed genomic evaluation of CSCM in Holstein cattle and suggests an unexpected genetic and allelic heterogeneity considering the mode of inheritance, as well as the type of variant. For the first time, we propose candidate causal variants that may explain bovine CSCM in a certain proportion of affected calves. We present cattle as a large animal model for human CMII and propose new genes and genomic variants as possible causes for related diseases in both animals and humans.
A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis
Authors: Chang Lisha , Ding Jie , Pu Juan , Zhu Jing , Zhou Xiang , Luo Qian , Li Jie , Qian Mengsen , Lin Shuhui , Li Juan , Wang Keming
Published: July 2024

Background

Metastasis is the leading cause of mortality in patients with colorectal cancer (CRC) and angiogenesis is a crucial factor in tumor invasion and metastasis. Long noncoding RNAs (lncRNAs) play regulatory functions in various biological processes in tumor cells, however, the roles of lncRNAs in CRC-associated angiogenesis remain to be elucidated in CRC, as do the underlying mechanisms.

Methods

We used bioinformatics to screen differentially expressed lncRNAs from TCGA database. LOC101928222 expression was assessed by qRT-PCR. The impact of LOC101928222 in CRC tumor development was assessed both in vitro and in vivo. The regulatory mechanisms of LOC101928222 in CRC were investigated by cellular fractionation, RNA-sequencing, mass spectrometric, RNA pull-down, RNA immunoprecipitation, RNA stability, and gene-specific m6A assays.

Results

LOC101928222 expression was upregulated in CRC and was correlated with a worse outcome. Moreover, LOC101928222 was shown to promote migration, invasion, and angiogenesis in CRC. Mechanistically, LOC101928222 synergized with IGF2BP1 to stabilize HMGCS2 mRNA through an m6A-dependent pathway, leading to increased cholesterol synthesis and, ultimately, the promotion of CRC development.

Conclusions

In summary, these findings demonstrate a novel, LOC101928222-based mechanism involved in the regulation of cholesterol synthesis and the metastatic potential of CRC. The LOC101928222-HMGCS2-cholesterol synthesis pathway may be an effective target for diagnosing and managing CRC metastasis.
Gut-derived immune cells and the gut-lung axis in ARDS
Authors: Ziaka Mairi , Exadaktylos Aristomenis
Published: July 2024

The gut serves as a vital immunological organ orchestrating immune responses and influencing distant mucosal sites, notably the respiratory mucosa. It is increasingly recognized as a central driver of critical illnesses, with intestinal hyperpermeability facilitating bacterial translocation, systemic inflammation, and organ damage. The “gut-lung” axis emerges as a pivotal pathway, where gut-derived injurious factors trigger acute lung injury (ALI) through the systemic circulation. Direct and indirect effects of gut microbiota significantly impact immune responses. Dysbiosis, particularly intestinal dysbiosis, termed as an imbalance of microbial species and a reduction in microbial diversity within certain bodily microbiomes, influences adaptive immune responses, including differentiating T regulatory cells (Tregs) and T helper 17 (Th17) cells, which are critical in various lung inflammatory conditions. Additionally, gut and bone marrow immune cells impact pulmonary immune activity, underscoring the complex gut-lung interplay. Moreover, lung microbiota alterations are implicated in diverse gut pathologies, affecting local and systemic immune landscapes. Notably, lung dysbiosis can reciprocally influence gut microbiota composition, indicating bidirectional gut-lung communication. In this review, we investigate the pathophysiology of ALI/acute respiratory distress syndrome (ARDS), elucidating the role of immune cells in the gut-lung axis based on recent experimental and clinical research. This exploration aims to enhance understanding of ALI/ARDS pathogenesis and to underscore the significance of gut-lung interactions in respiratory diseases.
Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients
Authors: Yang Xu , Liu Qing , Guo Zhiwei , Yang Xuexi , Li Kun , Han Bowei , Zhang Min , Sun Minying , Huang Limin , Cai Gengxi , Wu Yingsong
Published: July 2024

Background

Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer.

Method

First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy.

Results

The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response.

Conclusion

These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.
GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene
Authors: Subramanyan Lalitha Vaishnavi , Rasheed Suhail Ahmed Kabeer , Wang Lijin , Ghosh Sujoy , Ong Michelle Shi Ning , Lakshmanan Manikandan , Wang Mei , Casey Patrick J.
Published: July 2024

GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be involved in mediating several steps of cancer progression. Recent studies found that Gα13 can function as an oncogene and contributes to progression and metastasis of multiple tumor types, including ovarian, head and neck and prostate cancers. In most cases, Gα12 and Gα13, as closely related α-subunits in the subfamily, have similar cellular roles. However, in recent years their differences in signaling and function have started to emerge. We previously identified that Gα13 drives invasion of Triple Negative Breast Cancer (TNBC) cells in vitro. As a highly heterogenous disease with various well-defined molecular subtypes (ER+ /Her2−, ER+ /Her2+, Her2+, TNBC) and subtype associated outcomes, the function(s) of Gα13 beyond TNBC should be explored. Here, we report the finding that low expression of GNA13 is predictive of poorer survival in breast cancer, which challenges the conventional idea of Gα12/13 being universal oncogenes in solid tumors. Consistently, we found that Gα13 suppresses the proliferation in multiple ER+ breast cancer cell lines (MCF-7, ZR-75-1 and T47D). Loss of GNA13 expression drives cell proliferation, soft-agar colony formation and in vivo tumor formation in an orthotopic xenograft model. To evaluate the mechanism of Gα13 action, we performed RNA-sequencing analysis on these cell lines and found that loss of GNA13 results in the upregulation of MYC signaling pathways in ER+  breast cancer cells. Simultaneous silencing of MYC reversed the proliferative effect from the loss of GNA13, validating the role of MYC in Gα13 regulation of proliferation. Further, we found Gα13 regulates the expression of MYC, at both the transcript and protein level in an ERα dependent manner. Taken together, our study provides the first evidence for a tumor suppressive role for Gα13 in breast cancer cells and demonstrates for the first time the direct involvement of Gα13 in ER-dependent regulation of MYC signaling. With a few exceptions, elevated Gα13 levels are generally considered to be oncogenic, similar to Gα12. This study demonstrates an unexpected tumor suppressive role for Gα13 in ER+ breast cancer via regulation of MYC, suggesting that Gα13 can have subtype-dependent tumor suppressive roles in breast cancer.
PEMOCS: Evaluating the effects of a concept-guided, PErsonalised, MOtor-Cognitive exergame training on cognitive functions and gait in chronic Stroke—study protocol for a randomised controlled trial
Authors: Huber S.K. , Knols R.H. , Held J.P.O. , Betschart M. , de Bruin E.D.
Published: July 2024

Background

Many stroke survivors remain with residual cognitive and motor impairments despite receiving timely acute and sub-acute rehabilitation. This indicates that rehabilitation following stroke should be continuous to meet the needs of individual stroke patients. Both cognitive and motor functions are essential for mastering daily life and, therefore, should be aimed at with rehabilitation. Exergames, motor-cognitive exercises performed using video games, are an auspicious method to train both motor and cognitive functions and at the same time may foster the long-term motivation for training. This study aims to assess the effect of concept-guided, personalised, motor-cognitive exergame training on cognitive and motor functions in chronic stroke survivors.

Methods

This study is a single-blinded, randomised controlled trial. Assessments are performed at baseline, after a 12-week intervention, and at a 24-weeks follow-up. Chronic stroke patients (≥ 18 years old, ≥ 6 months post-stroke) able to stand for 3 min, independently walk 10 m, follow a two-stage command, and without other neurological diseases apart from cognitive deficits or dementia are included. Participants in the intervention group perform the exergame training twice per week for 30 (beginning) up to 40 (end) minutes additionally to their usual care programme. Participants in the control group receive usual care without additional intervention(s). Global cognitive functioning (total Montreal Cognitive Assessment (MoCA) score) is the primary outcome. Secondary outcomes include health-related quality of life, specific cognitive functions, single- and dual-task mobility, and spatiotemporal gait parameters. The target sample size for this trial is 38 participants. Linear mixed models with the post-outcome scores as dependent variables and group and time as fixed effects will be performed for analysis.

Discussion

Superior improvements in global cognitive functioning and in the abovementioned secondary outcomes in the intervention group compared to the control group are hypothesised. The results of this study may guide future design of long-term rehabilitation interventions after stroke.

Trial registration

ClinicalTrials.gov (NCT05524727). Registered on September 1, 2022.
6-Bromo quinazoline derivatives as cytotoxic agents: design, synthesis, molecular docking and MD simulation
Authors: Emami Leila , Hassani Maryam , Mardaneh Pegah , Zare Fateme , saeedi Maryam , Emami Mina , Khabnadideh Soghra , Sadeghian Sara
Published: July 2024

Based on unselectively, several side effects and drug resistance of available anticancer agents, the development and research for novel anticancer agents is necessary. In this study, a new series of quinazoline-4(3H)-one derivatives having a thiol group at position 2 of the quinazoline ring (8a-8 h) were designed and synthesized as potential anticancer agents. The Chemical structures of all compounds were characterized by 1H-NMR, 13C-NMR, and Mass spectroscopy. The antiproliferative activity of all derivatives were determined against two cancer cell lines (MCF-7 and SW480) and one normal cell lines (MRC-5) by the MTT method. Cisplatin, Erlotinib and Doxorubicin were used as positive controls. The results of in vitro screening showed that 8a with an aliphatic linker to SH group was the most potent compound with IC50 values of 15.85 ± 3.32 and 17.85 ± 0.92 µM against MCF-7 and SW480 cell lines, respectively. 8a indicated significantly better potency compared to Erlotinib in the MCF-7 cell line. The cytotoxic results obtained from testing compound 8a on the normal cell line, revealing an IC50 value of 84.20 ± 1.72 µM, provide compelling evidence of its selectivity in distinguishing between tumorigenic and non-tumorigenic cell lines. Structure–activity relationship indicated that the variation in the anticancer activities of quinazoline-4(3H)-one derivatives was affected by different substitutions on the SH position. Molecular docking and MD simulation were carried out for consideration of the binding affinity of compounds against EGFR and EGFR-mutated. The binding energy of compounds 8a and 8c were calculated at -6.7 and − 5.3 kcal.mol− 1, respectively. Compounds 8a and 8c were found to establish hydrogen bonds and some other important interactions with key residue. The DFT analysis was also performed at the B3LYP/6–31 + G(d, p) level for compounds 8a, 8c and Erlotinib. Compound 8a was thermodynamically more stable than 8c. Also, the calculated theoretical and experimental data for the IR spectrum were in agreement. The obtained results delineated that the 8a can be considered an appropriate pharmacophore to develop as an anti-proliferative agent.
Clostridium perfringens in central Colombia: frequency, toxin genes, and risk factors
Authors: Camargo Anny , Bohorquez Laura , López Diana Paola , Ferrebuz-Cardozo Atilio , Castellanos-Rozo José , Díaz-Ovalle Javier , Rada Mariana , Camargo Milena , Ramírez Juan David , Muñoz Marina
Published: July 2024

Clostridium perfringens is an opportunistic bacterium that causes intestinal diseases in both humans and animals. This study aimed to assess the frequency of C. perfringens and the presence of toxin-encoding genes in fecal samples from individuals with or without gastrointestinal symptoms in the Department of Boyacá, Colombia. Additionally, risk factors associated with carriage and disease development were analyzed. A total of 114 stool samples were analyzed using a molecular test based on specific polymerase chain reaction (PCR) targeting 16S-rRNA and alpha toxin (cpa) genes. For individuals with a positive result for the PCR test, stool samples were cultured on Tryptose Sulfite Cycloserine (TSC) agar. Two to five colonies forming units were selected based on phenotypic characteristics, resulting in 56 bacterial isolates. These isolates were then analyzed for toxin-coding genes associated with gastrointestinal diseases. In addition, sociodemographic and clinical data from 77 individuals were also analyzed. The overall frequency of C. perfringens was 19.3% (n = 22/114). The detection frequency in 77 individuals with clinical data was 16.6% (n = 5/30) among symptomatic individuals and 21.2% (n = 10/47) among asymptomatic individuals. All 56 isolates obtained carried the cpa gene, while cpb2 was present in 10.7% (n = 6/56); cpe and cpb genes were not detected. Notably, diabetes and autoimmune diseases are significantly associated with an increased risk of C. perfringens detection (adjusted OR 8.41: 95% CI 1.32–35.89). This study highlights an elevated frequency of C. perfringens and the presence of the cpb2 gene in asymptomatic individuals compared with their symptomatic counterparts. These findings offer insights into the distribution and virulence factors of C. perfringens at a micro-geographical level. This information supports the need for developing tailored prevention strategies based on local characteristics to promote active surveillance programs based on molecular epidemiology.
Gut microbiota shifts from onset to remission in immune checkpoint inhibitor-induced enterocolitis: a case report
Authors: Hirata Yuki , Tanaka Yoshiki , Yokota Haruka , Ohno Hiroshi , Nishida Koji , Shimizu Hikaru , Mizuta Noboru , Nakazawa Kei , Koshiba Ryoji , Kakimoto Kazuki , Miyazaki Takako , Nakamura Shiro , Nishikawa Hiroki
Published: July 2024

Background

Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. Case presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations.

Conclusions

Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.
The chromatin accessibility and transcriptomic landscape of the aging mice cochlea and the identification of potential functional super-enhancers in age-related hearing loss
Authors: Zhang Chanyuan , Yang Ting , Luo Xiaoqin , Zhou Xiaoqing , Feng Menglong , Yuan Wei
Published: July 2024

Background

Presbycusis, also referred to as age-related hearing loss (ARHL), is a condition that results from the cumulative effects of aging on an individual's auditory capabilities. Given the limited understanding of epigenetic mechanisms in ARHL, our research focuses on alterations in chromatin-accessible regions.

Methods

We employed assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) in conjunction with unique identifier (UID) mRNA-seq between young and aging cochleae, and conducted integrated analysis as well as motif/TF-gene prediction. Additionally, the essential role of super-enhancers (SEs) in the development of ARHL was identified by comparative analysis to previous research. Meanwhile, an ARHL mouse model and an aging mimic hair cell (HC) model were established with a comprehensive identification of senescence phenotypes to access the role of SEs in ARHL progression.

Results

The control cochlear tissue exhibited greater chromatin accessibility than cochlear tissue affected by ARHL. Furthermore, the levels of histone 3 lysine 27 acetylation were significantly depressed in both aging cochlea and aging mimic HEI-OC1 cells, highlighting the essential role of SEs in the development of ARHL. The potential senescence-associated super-enhancers (SASEs) of ARHL were identified, most of which exhibited decreased chromatin accessibility. The majority of genes related to the SASEs showed obvious decreases in mRNA expression level in aging HCs and was noticeably altered following treatment with JQ1 (a commonly used SE inhibitor).

Conclusion

The chromatin accessibility in control cochlear tissue was higher than that in cochlear tissue affected by ARHL. Potential SEs involved in ARHL were identified, which might provide a basis for future therapeutics targeting SASEs related to ARHL.