bluuebunny/crossref_metadata_2025 huggingface dataset:
Powered single hip joint exoskeletons for gait rehabilitation: a systematic review and Meta-analysis
Authors: Daliri Mahla , Ghorbani Mohammad , Akbarzadeh Alireza , Negahban Hossein , Ebrahimzadeh Mohammad H , Rahmanipour Elham , Moradi Ali
Published: January 2024

Background

Gait disorders and as a consequence, robotic rehabilitation techniques are becoming increasingly prevalent as the population ages. In the area of rehabilitation robotics, using lightweight single hip joint exoskeletons are of significance. Considering no prior systematic review article on clinical outcomes, we aim to systematically review powered hip exoskeletons in terms of gait parameters and metabolic expenditure effects.

Methods

Three databases of PubMed, Scopus, and Web of science were searched for clinical articles comparing outcomes of gait rehabilitation using hip motorized exoskeleton with conventional methods, on patients with gait disorder or healthy individuals. Of total number of 37 reviewed articles, 14 trials were quantitatively analyzed. Analyses performed in terms of gait spatiotemporal parameters like speed (self-speed and maximum speed), step length, stride length, cadence, and oxygen consumption.

Results

Improved clinical outcomes of gait spatiotemporal parameters with hip joint exoskeletons are what our review’s findings show. In terms of gait values, meta-analysis indicates that rehabilitation with single hip joint exoskeleton enhanced parameters of maximum speed by 0.13 m/s (0.10–0.17) and step length by 0.06 m (0.05–0.07). For the remaining investigated gait parameters, no statistically significant difference was observed. Regarding metabolic parameters, oxygen consumption was lower in individuals treated with hip exoskeleton (− 1.23 ml/min/kg; range − 2.13 to − 0.32).

Conclusion

Although the analysis demonstrated improvement with just specific gait measures utilizing powered hip exoskeletons, the lack of improvement in all parameters is likely caused by the high patient condition heterogeneity among the evaluated articles. We also noted in patients who rehabilitated with the hip exoskeleton, the oxygen cost was lower. More randomized controlled trials are needed to verify both the short- and long-term clinical outcomes, including patient-reported measures.

Level of evidence

Level I (systematic review and meta-analysis).
The impact of primary total hip and knee replacement on frailty: an observational prospective analysis
Authors: Kappenschneider Tobias , Bammert Philip , Maderbacher Günther , Greimel Felix , Parik Lukas , Holzapfel Dominik Emanuel , Schraag Amadeus Dominik , Götz Julia , Michalk Katrin , Grifka Joachim , Meyer Matthias
Published: January 2024

Background

Osteoarthritis is a prevalent condition in frail older adults that requires hip or knee replacement in many patients. The aim of the study was to determine the impact of hip and knee arthroplasty on frailty.

Methods

In this prospective short-term study, we used data from 101 participants of the ongoing Special Orthopaedic Geriatrics (SOG) trial, funded by the German Federal Joint Committee (GBA). Frailty, measured by Fried’s Physical Frailty Phenotype (PFP), was assessed preoperatively, 7 days postoperatively, 4–6 weeks and 3 months after hip and knee arthroplasty. ANOVA with repeated measures and post-hoc tests for the subgroups were used for the statistical analysis.

Results

Of the 101 participants, 50 were pre-frail (1–2 PFP criteria) and 51 were frail (≥ 3 PFP criteria) preoperatively. In the pre-frail group, the PFP score decreased from 1.56 ± 0.50 (median 2) preoperatively to 0.53 ± 0.73 (median 0) 3 months after surgery (p < 0.001). The PFP score in the frail cohort decreased from 3.39 ± 1.45 (median 3) preoperatively to 1.27 ± 1.14 (median 1) 3 months postoperatively (p < 0.001). While the PFP score of the pre-frail participants increased 7 days after surgery, the PFP score of the frail group decreased significantly.

Conclusion

Pre-frail individuals often regain robustness and patients with frailty are no longer assessed as frail after surgery. Joint replacement is an effective intervention to improve frailty in hip and knee osteoarthritis.

Trial registration

This study is part of the Special Orthopaedic Geriatrics (SOG) trial, German Clinical Trials Register DRKS00024102. Registered on 19 January 2021.
Vitamin intake and periodontal disease: a meta-analysis of observational studies
Authors: Mi Nannan , Zhang Miaomiao , Ying Zheng , Lin Xiaoping , Jin Ying
Published: January 2024

Objective

A meta-analysis was performed to assess the epidemiological correlation between dietary intake of various types of vitamin intake and the risk of periodontal disease.

Methods

A comprehensive computerized search was conducted in eight databases, namely PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine Disc, CNKI, VIP, and WanFang Database, and a random effect model was applied to combine pooled odds ratio (ORs) with corresponding 95% confidence intervals (CIs) of the included studies, and the sensitivity analysis was performed to explore the impact of a single study on the comprehensive results.

Results

We finally included 45 effect groups from 23 observational studies, with a total number of study participants of 74,488. The results showed that higher levels of vitamin A (OR: 0.788, 95% CI: 0.640–0.971), vitamin B complex (OR: 0.884, 95% CI: 0.824–0.948), vitamin C (OR: 0.875, 95% CI: 0.775–0.988), vitamin D (OR: 0.964, 95% CI: 0.948–0.981), and vitamin E (OR: 0.868, 95% CI: 0.776–0.971) intake all were negatively correlated with periodontal disease. After removing each study, leave-one-out sensitivity analysis indicated no significant change in the overall results of any of the five meta-analyses.

Conclusions

The results from this meta-analysis demonstrated a negative association between high-dose vitamin A, vitamin B complex, vitamin C, vitamin D, and vitamin E consumption and the likelihood of developing periodontal disease, revealing the significant role of vitamins in preventing periodontal disease.
The effect of increasing the gaps between the front teeth on torque and intrusion control of the incisors for anterior retraction with clear aligners: a prospective study
Authors: Li Ni , Lei Xiao , Cao Yuan , Liu Lu , Zhang Yanqi , Ning Qiang , Gui Linyuan , Jin Fang
Published: January 2024

Objective

To investigate the effect of sequential distalization on increasing gaps in the maxillary anterior teeth, focusing on the control of torque and three-dimensional teeth movement during anterior retraction with clear aligners in extraction cases.

Methods

We recruited 24 patients who were undergoing extraction bilateral maxillary first premolars with clear aligners. According to a predetermined increment in the spaces between the maxillary anterior teeth, the patients were divided into three groups: those with no gap (9 cases), a 0.5 mm gap (6 cases) and a 1.0 mm gap (9 cases). In each group, a 2.0 mm en-mass retraction was applied on the anterior teeth. Plaster casts of the upper full dentition were obtained both before and after a 2 mm retraction. The palatal folds were used to overlap each pair of models. The three-dimensional movement of the teeth and the change of torque for the anterior teeth were subsequently analyzed using Geomagic Studio 2014 software.

Results

The change in torque in the groups with added gaps was significantly smaller than that in the group with no gaps (P < 0.05). There was no significant difference in this respect when comparing the group with a 0.5 mm gap added to the group with a 1.0 mm gap was added (P > 0.05). In the labial-lingual and vertical directions, the displacements of the central and lateral incisors were smaller in the groups with additional gaps compared to those in the groups without gaps (P < 0.05). However, there was no significant difference observed when comparing the group with a 0.5 mm added gap to the group with a 1.0 mm added gap (P > 0.05). Then, a comparison was made between the displacement of the second premolar to the second molar in the mesial-distal direction across all groups. The study revealed that the anchorage molars in the group without gaps demonstrated significantly smaller displacement compared to those in the group with additional gaps (P < 0.05).

Conclusion

Advantages were observed in controlling the torque of the anterior teeth and achieving a desired pattern closer to normal bodily movement by sequentially distalizing the maxillary anterior teeth gaps. Increasing the gaps between the maxillary anterior teeth also resulted in improved control of the vertical direction of the anterior teeth. However, this retraction strategy necessitates substantial protection of the anchorage molars.
Translation and validation into Spanish of the oral health self-efficacy scale in Chilean older adults
Authors: Muñoz-Sepúlveda Fernanda , Acevedo Claudia , Mariño Rodrigo , Sanzana-Luengo Cristina , Navarro Pablo , Beltrán Víctor
Published: January 2024

Background

Population ageing poses a challenge to improving the well-being of older adults, particularly in terms of oral health. Promoting self-efficacy in oral health behaviours is crucial for maintaining this population’s health and quality of life. The Oral Health Self-Efficacy Scale (OHSES) has been widely used to assess dental self-efficacy and is considered comprehensive and reliable. However, there is a need to validate OHSES for Spanish-speaking older adults. This study aimed to assess the reliability and validity of the translated questionnaire for use in the older Chilean population.

Methods

A sample of 188 older adults, aged 60 years and above residing independently in the community, were recruited by accessing databases from the National Senior Citizen Service and various community organisations within the region of La Araucanía. The participants underwent comprehensive oral examinations and oral health interviews, focusing on variables such as OHSES, Oral health-related quality of life (OHIP-14Sp), assessment of remaining teeth, knowledge and attitudes toward oral health, and sociodemographic characteristics. The validity of the translated questionnaire was assessed through translation and cross-cultural adaptation, cognitive debriefing, and face and content validation. The psychometric properties of the questionnaire were evaluated through measures of internal consistency (Cronbach’s alpha), content validity (Content validity index), construct validity (factor analysis and Pearson correlation analysis), and test-retest reliability (intraclass correlation).

Results

The Spanish version of OHSES demonstrated adequate face and content validity. The confirmatory factor analysis confirmed a two-factor scale with 7 items for a better fit. The scale demonstrated high internal consistency (Cronbach’s alpha = 0.821) and acceptable test–retest reliability (ICC = 0.411). Correlations were found between the OHSES score, the number of remaining teeth, knowledge and attitudes towards oral health, and the OHIP-14Sp (p < 0.01).

Conclusions

This study confirms the validity of the Spanish version of the Oral Health Self-Efficacy Scale for older adults in Chile. The scale is expected to be helpful in assessing self-efficacy in dental interventions and collecting data for international comparisons. This research opens new dimensions in patient-reported assessment of oral health.
Evaluation of the genotoxicity, cytotoxicity, and bioactivity of calcium silicate-based cements
Authors: Esen Merve , Guven Yeliz , Seyhan Mehmet Fatih , Ersev Handan , Tuna-Ince Elif Bahar
Published: January 2024

Background

As calcium silicate-based cements (CSCs) have found success in various vital pulp therapy applications, several new CSC products have emerged. This study aimed to assess the genotoxicity, cytotoxicity, and bioactivity of four CSCs by comparing the newly introduced materials Bio MTA+ and MTA Cem with previously studied materials, Biodentine and NeoMTA.

Methods

Genotoxicity was evaluated using the micronucleus (MN) assay in human peripheral blood lymphocyte cells, measuring MN frequency and nuclear division index (NDI). Cytotoxicity was assessed in human dental pulp stem cells through the Water-Soluble Tetrazolium Salt-1 (WST-1) colorimetric assay. Bioactivity was determined by ELISA, measuring the levels of angiogenic and odontogenic markers (BMP-2, FGF-2, VEGF, and ALP). Statistical analyses included ANOVA, Dunnet and Sidak tests, and Wald chi-square test. (p < .05).

Results

The MN frequency in the groups was significantly lower than that in the positive control group (tetraconazole) (p < .05). NDI values decreased with increasing concentration (p < .05). Bio MTA+ and NeoMTA showed decreased cell viability at all concentrations in 7-day cultures (p < .01). All materials increased BMP-2, FGF-2, and VEGF levels, with Biodentine and NeoMTA showing the highest levels of BMP-2 and FGF-2 on day 7. Biodentine displayed the highest VEGF levels on day 7. Biodentine and NeoMTA groups exhibited significantly higher ALP activity than the Bio MTA+ and MTA Cem groups by day 7.

Conclusion

Bio MTA+ and MTA Cem demonstrated no genotoxic or cytotoxic effects. Moreover, this study revealed bioactive potentials of Bio MTA+ and MTA Cem by enhancing the expression of angiogenic and osteogenic growth factors.
The effects of rhythmic auditory stimulation on functional ambulation after stroke: a systematic review
Authors: Gonzalez-Hoelling Samira , Reig-García Gloria , Bertran-Noguer Carme , Suñer-Soler Rosa
Published: January 2024

Background

Several studies have reported the effect of rhythmic auditory stimulation (RAS) on functional ambulation in stroke patients, yet no systematic overview has yet been published. This study aims to synthesize the available evidence describing changes in stroke patients after RAS intervention for functional ambulation and the use of walking assistive devices, and to find out if the effect of RAS and music-based RAS differs depending on the lesioned area.

Methods

The PubMed, PEDro, Cochrane Central Register of Controlled Trials, Web of Science, Scopus and CINAHL electronic databases were searched for reports evaluating the effect of RAS on walking in stroke patients, applying the PICOS criteria for the inclusion of studies.

Results

Twenty one articles were included (948 stroke survivors). Most studies were of good methodological quality according to the PEDro scale, but they had a high risk of bias. The most consistent finding was that RAS improves walking and balance parameters in stroke patients in all phases compared to baseline and versus control groups with conventional treatment. Functional ambulation and the use of walking assistive devices were inconsistently reported. Several studies also suggest that RAS may be as good as other complementary therapies (horse-riding and visual cueing).

Conclusions

Despite the beneficial effects of RAS, the question remains as to whether it is better than other complementary therapies. Given the heterogeneity of the interventions, the interventions in control groups, the varied durations, and the different outcome measures, we suggest that care should be taken in interpreting and generalizing findings.

PROSPERO Registration

CRD42021277940.
Mechanisms predictive of Tibetan Medicine Sophora moorcroftiana alkaloids for treatment of lung cancer based on the network pharmacology and molecular docking
Authors: Ji Peng , Zhao Nian-Shou , Wu Fan-Lin , Wei Yan-Ming , Laba Ci-Dan , Wujin Cuo-Mu , Hua Yong-Li , Yuan Zi-Wen , Yao Wan-Ling
Published: January 2024

Background

Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance.

Methods

The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets – LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding.

Results

We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells.

Conclusions

Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.
Baicalin enhances proliferation and reduces inflammatory-oxidative stress effect in H2O2-induced granulosa cells apoptosis via USP48 protein regulation
Authors: Chen Jun , Lin Chuhua , Huang Xiurong , Bian Wei
Published: January 2024

Background

Oxidative stress and inflammation can lead to apoptosis of ovarian granulosa cells (GCs), resulting in ovulation disorders and infertility. Baicalin (BAI) promotes cell proliferation and reduces inflammation and oxidative stress. However, the mechanisms by which BAI treatment affects oxidative stress and inflammation in GCs remain incompletely understood.

Methods

KGN cells were treated with hydrogen peroxide (H2O2) to analyze the effect of oxidative stress on GCs in vitro. Subsequently, H2O2-stimulated KGN cells were treated with BAI. The levels of GSH-Px, CAT, and SOD were measured using an activity assay kit. The levels of MDA, IL-1β, IL-6, IL-8, and TNF-α were measured by ELISA. Proliferation, apoptosis, and mRNA and protein levels were measured using the CCK8, flow cytometry, qRT-PCR, and western blotting.

Results

H2O2 treatment inhibited KGN cell proliferation and promoted apoptosis, accompanied by increased oxidative stress and inflammation. BAI promoted proliferation, inhibited apoptosis, and reduced oxidative stress and inflammation in H2O2-stimulated KGN cells. BAI treatment promoted USP48 protein expression, and USP48 knockdown abrogated the protective effects of BAI, indicating that USP48 is a downstream mediator of BAI.

Conclusion

BAI treatment enhanced cell proliferation and ameliorated oxidative stress and inflammation by enhancing USP48 protein expression. BAI, which is used clinically and as a dietary supplement, may alleviate oxidative stress-induced GC injury and ovarian disorders.
Modulation of temporal and occipital cortex by acupuncture in non-menstrual MWoA patients: a rest BOLD fMRI study
Authors: Yang Yu-Chan , Wei Xiang-Yu , Zhang Ying-Ying , Xu Chun-Yang , Cheng Jian-Ming , Gong Zhi-Gang , Chen Hui , Huang Yan-Wen , Yuan Jie , Xu Hui-Hui , Wang Hui , Zhan Song-Hua , Tan Wen-Li
Published: January 2024

Objective

To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI).

Methods

Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed.

Results

Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008).

Conclusion

Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.
Outer packaging labelling of medicines in Southern African Development Community (SADC) countries: comparative analysis of requirements and transition terms for harmonisation
Authors: Narsai K. , Masekela F. B. , Leufkens H. G.M , Mantel-Teeuwisse A. K.
Published: January 2024

Introduction

The COVID-19 pandemic highlighted an urgent need for harmonised requirements for the regulation of medicines. To fully implement harmonised medicines regulations across Africa, common technical standards of medicine regulations are needed. One such technical standard is the labelling of medicines on outer packaging. In this study, we compared outer packaging labelling requirements and transition terms for harmonization for countries in the Southern African Development Community (SADC) region.

Methods

Data on legislation and/or regulatory guidelines for medicine outer packaging labelling from National Medicines Regulatory Authorities (NMRAs) were obtained for countries in the SADC region (n = 16) by February 2023. A detailed comparative content analysis was conducted to determine alignment with the requirements of the Southern African Development Community (SADC) harmonised labelling guidelines to assess readiness levels of each country to transition to the SADC harmonised labelling guideline for outer packaging of medicines.

Results

Content analysis showed at least 11 out of 16 countries require national legal reform to transition to the SADC harmonised labelling guideline. In all cases where countries specified labelling requirements for outer packaging of medicines, these were stipulated in national medicines legislation.

Conclusion

Even though there is a high level of alignment across the countries in terms of national labelling requirements, most countries in the SADC region would still require national legislative reform to transition to regional harmonised labelling requirements and then ultimately to continental requirements of the African Medicines Agency (AMA).
An abattoir study of the prevalence of foot lesions and claw measurements in water buffalo in Egypt
Authors: Salem Shebl E. , Refaai Walid , Abd EL Raouf Mustafa , Hamed Mohamed A. , Ezzeldein Shimaa A. , Eisa Eslam F. , Mesalam Ayman , Maddox Thomas W. , Monir Ahmed
Published: January 2024

Background

Lameness has been associated with compromised animal welfare and reduced productivity in dairy cattle herds worldwide. However, little is known about the prevalence of claw lesions in the dairy buffalo population in Egypt. Furthermore, the optimum measurements for claw trimming in buffalo are unknown. A cross-sectional cadaver study was conducted where 135 pair buffalo hind feet were collected from 4 slaughterhouses and examined for the presence of claw lesions. The proportion and associated 95% confidence interval (CI) of each type of lesion were calculated. A separate set of healthy claws (n = 26) underwent ultrasonography (US) and computed tomography (CT). The agreement between US and CT measurements was assessed using Passing-Bablok regression and intraclass correlation coefficient. The CT measurements were used to calculate trimming recommendations.

Results

At least one lesion was identified in 242 claws (89.6%, 95% CI = 85.4–93.0). In healthy claws, poor to moderate agreement was identified between US and CT measurements which could be due a sample size of the study. The average ± standard deviation (SD) minimum recommended external wall length of the lateral and medial claws in heifers was 7.1 ± 0.36 cm and 7.5 ± 0.35 cm, respectively. The average ± SD minimum recommended external wall length in buffaloes over five years of age was 8.2 ± 0.27 cm and 8.4 ± 0.39 cm for the lateral and medial claws, respectively.

Conclusions

The study found a high prevalence of claw lesions in buffalo in Egypt, the clinical significance of which requires further elucidation. Recommended measurements will help guide claw trimming in buffalo to minimise lesions.
Physiology and pharmacological targeting of phase separation
Authors: Wang Fangfang , Zhang Youwei
Published: January 2024

Liquid–liquid phase separation (LLPS) in biology describes a process by which proteins form membraneless condensates within a cellular compartment when conditions are met, including the concentration and posttranslational modifications of the protein components, the condition of the aqueous solution (pH, ionic strength, pressure, and temperature), and the existence of assisting factors (such as RNAs or other proteins). In these supramolecular liquid droplet-like inclusion bodies, molecules are held together through weak intermolecular and/or intramolecular interactions. With the aid of LLPS, cells can assemble functional sub-units within a given cellular compartment by enriching or excluding specific factors, modulating cellular function, and rapidly responding to environmental or physiological cues. Hence, LLPS is emerging as an important means to regulate biology and physiology. Yet, excessive inclusion body formation by, for instance, higher-than-normal concentrations or mutant forms of the protein components could result in the conversion from dynamic liquid condensates into more rigid gel- or solid-like aggregates, leading to the disruption of the organelle’s function followed by the development of human disorders like neurodegenerative diseases. In summary, well-controlled formation and de-formation of LLPS is critical for normal biology and physiology from single cells to individual organisms, whereas abnormal LLPS is involved in the pathophysiology of human diseases. In turn, targeting these aggregates or their formation represents a promising approach in treating diseases driven by abnormal LLPS including those neurodegenerative diseases that lack effective therapies.
Assessment of wood smoke induced pulmonary toxicity in normal- and chronic bronchitis-like bronchial and alveolar lung mucosa models at air–liquid interface
Authors: Upadhyay Swapna , Rahman Mizanur , Rinaldi Selina , Koelmel Jeremy , Lin Elizabeth Z. , Mahesh Padukudru Anand , Beckers Johannes , Johanson Gunnar , Pollitt Krystal J. Godri , Palmberg Lena , Irmler Martin , Ganguly Koustav
Published: January 2024

Background

Chronic obstructive pulmonary disease (COPD) has the highest increased risk due to household air pollution arising from biomass fuel burning. However, knowledge on COPD patho-mechanisms is mainly limited to tobacco smoke exposure. In this study, a repeated direct wood smoke (WS) exposure was performed using normal- (bro-ALI) and chronic bronchitis-like bronchial (bro-ALI-CB), and alveolar (alv-ALI) lung mucosa models at air–liquid interface (ALI) to assess broad toxicological end points.

Methods

The bro-ALI and bro-ALI-CB models were developed using human primary bronchial epithelial cells and the alv-ALI model was developed using a representative type-II pneumocyte cell line. The lung models were exposed to WS (10 min/exposure; 5-exposures over 3-days; n = 6–7 independent experiments). Sham exposed samples served as control. WS composition was analyzed following passive sampling. Cytotoxicity, total cellular reactive oxygen species (ROS) and stress responsive NFkB were assessed by flow cytometry. WS exposure induced changes in gene expression were evaluated by RNA-seq (p ≤ 0.01) followed by pathway enrichment analysis. Secreted levels of proinflammatory cytokines were assessed in the basal media. Non-parametric statistical analysis was performed.

Results

147 unique compounds were annotated in WS of which 42 compounds have inhalation toxicity (9 very high). WS exposure resulted in significantly increased ROS in bro-ALI (11.2%) and bro-ALI-CB (25.7%) along with correspondingly increased NFkB levels (bro-ALI: 35.6%; bro-ALI-CB: 18.1%). A total of 1262 (817-up and 445-down), 329 (141-up and 188-down), and 102 (33-up and 69-down) genes were differentially regulated in the WS-exposed bro-ALI, bro-ALI-CB, and alv-ALI models respectively. The enriched pathways included the terms acute phase response, mitochondrial dysfunction, inflammation, oxidative stress, NFkB, ROS, xenobiotic metabolism of AHR, and chronic respiratory disorder. The enrichment of the ‘cilium’ related genes was predominant in the WS-exposed bro-ALI (180-up and 7-down). The pathways primary ciliary dyskinesia, ciliopathy, and ciliary movement were enriched in both WS-exposed bro-ALI and bro-ALI-CB. Interleukin-6 and tumor necrosis factor-α were reduced (p < 0.05) in WS-exposed bro-ALI and bro-ALI-CB.

Conclusion

Findings of this study indicate differential response to WS-exposure in different lung regions and in chronic bronchitis, a condition commonly associated with COPD. Further, the data suggests ciliopathy as a candidate pathway in relation to WS-exposure.
Itaconate Production from Crude Substrates with U. maydis: Scale-up of an Industrially Relevant Bioprocess
Authors: Helm Tabea , Stausberg Thilo , Previati Martina , Ernst Philipp , Klein Bianca , Busche Tobias , Kalinowski Jörn , Wibberg Daniel , Wiechert Wolfgang , Claerhout Lien , Wierckx Nick , Noack Stephan
Published: January 2024

Background

Industrial by-products accrue in most agricultural or food-related production processes, but additional value chains have already been established for many of them. Crude glycerol has a 60% lower market value than commercial glucose, as large quantities are produced in the biodiesel industry, but its valorisation is still underutilized. Due to its high carbon content and the natural ability of many microorganisms to metabolise it, microbial upcycling is a suitable option for this waste product.

Results

In this work, the use of crude glycerol for the production of the value-added compound itaconate is demonstrated using the smut fungus Ustilago maydis. Starting with a highly engineered strain, itaconate production from an industrial glycerol waste stream was quickly established on a small scale, and the resulting yields were already competitive with processes using commercial sugars. Adaptive laboratory evolution resulted in an evolved strain with a 72% increased growth rate on glycerol. In the subsequent development and optimisation of a fed-batch process on a 1.5-2 L scale, the use of molasses, a side stream of sugar beet processing, eliminated the need for other expensive media components such as nitrogen or vitamins for biomass growth. The optimised process was scaled up to 150 L, achieving an overall titre of 72 g L− 1, a yield of 0.34 g g− 1, and a productivity of 0.54 g L− 1 h− 1.

Conclusions

Pilot-scale itaconate production from the complementary waste streams molasses and glycerol has been successfully established. In addition to achieving competitive performance indicators, the proposed dual feedstock strategy offers lower process costs and carbon footprint for the production of bio-based itaconate.
Highly selective whole-cell 25-hydroxyvitamin D3 synthesis using molybdenum-dependent C25-steroid dehydrogenase and cyclodextrin recycling
Authors: Kosian Dennis , Willistein Max , Weßbecher Ralf , Eggers Constantin , May Oliver , Boll Matthias
Published: January 2024

Background

The global prevalence of vitamin D (VitD) deficiency associated with numerous acute and chronic diseases has led to strategies to improve the VitD status through dietary intake of VitD-fortified foods and VitD supplementation. In this context, the circulating form of VitD3 (cholecalciferol) in the human body, 25-hydroxy-VitD3 (calcifediol, 25OHVitD3), has a much higher efficacy in improving the VitD status, which has motivated researchers to develop methods for its effective and sustainable synthesis. Conventional monooxygenase-/peroxygenase-based biocatalytic platforms for the conversion of VitD3 to value-added 25OHVitD3 are generally limited by a low selectivity and yield, costly reliance on cyclodextrins and electron donor systems, or by the use of toxic co-substrates.

Results

In this study, we used a whole-cell approach for biocatalytic 25OHVitD3 synthesis, in which a molybdenum-dependent steroid C25 dehydrogenase was produced in the denitrifying bacterium Thauera aromatica under semi-aerobic conditions, where the activity of the enzyme remained stable. This enzyme uses water as a highly selective VitD3 hydroxylating agent and is independent of an electron donor system. High density suspensions of resting cells producing steroid C25 dehydrogenase catalysed the conversion of VitD3 to 25OHVitD3 using either O2 via the endogenous respiratory chain or externally added ferricyanide as low cost electron acceptor. The maximum 25OHVitD3 titer achieved was 1.85 g L–1 within 50 h with a yield of 99%, which is 2.2 times higher than the highest reported value obtained with previous biocatalytic systems. In addition, we developed a simple method for the recycling of the costly VitD3 solubiliser cyclodextrin, which could be reused for 10 reaction cycles without a significant loss of quality or quantity.

Conclusions

The established steroid C25 dehydrogenase-based whole-cell system for the value-adding conversion of VitD3 to 25OHVitD3 offers a number of advantages in comparison to conventional oxygenase-/peroxygenase-based systems including its high selectivity, independence from an electron donor system, and the higher product titer and yield. Together with the established cyclodextrin recycling procedure, the established system provides an attractive platform for large-scale 25OHVitD3 synthesis.
B cells in head and neck squamous cell carcinoma: current opinion and novel therapy
Authors: Guo Xinyue , Xu Licheng , Nie Luan , Zhang Chenyu , Liu Yaohui , Zhao Rui , Cao Jing , Tian Linli , Liu Ming
Published: January 2024

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC.
Methionine enkephalin (MENK) protected macrophages from ferroptosis by downregulating HMOX1 and ferritin
Authors: Tian Jing , Fu Wenrui , Xie Zifeng , Zhao Yuanlong , Yang Haochen , Zhao Jiafan
Published: January 2024

Objective

The aim of this work was to investigate the immunological effect of MENK by analyzing the protein spectrum and bioinformatics of macrophage RAW264.7, and to explore the relationship between macrophage and ferroptosis.

Result

We employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages and macrophages intervened by MENK. A total of 208 DEPs were identified. Among these, 96 proteins had upregulated expression and 112 proteins had downregulated expression. Proteomic analysis revealed a significant enrichment of DEPs associated with iron metabolism. The identification of hub genes was conducted using KEGG pathway diagrams and protein-protein interaction (PPI) analysis. The hub genes identified in this study include HMOX1 and Ferritin (FTH and FTL). A correlation was established between HMOX1, FTH, and FTL in the GO and KEGG databases. The results of PCR, WB and immunofluorescence showed that MENK downregulated the level of HMOX1 and FTH.

Conclusion

MENK had the potential to become an adjuvant chemotherapy drug by regulating iron metabolism in macrophages, reducing levels of HMOX1 and ferritin. We proposed an innovative research direction on the therapeutic potential of MENK, focusing on the relationship between ferroptosis and macrophage activity.
Serum erythropoietin level is increased during stimulation for IVF but not in OHSS
Authors: Rekola Merituuli , Korhonen Kati , Unkila-Kallio Leila , Alfthan Henrik , Stefanovic Vedran , Tiitinen Aila , Mikkola Tomi S. , Savolainen-Peltonen Hanna
Published: January 2024

Background

Erythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS).

Methods

24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo.

Results

During IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2–13.4 IU/L and 12.5; 10.3–13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4–19.2 IU/L vs. 10.2; 8.8–12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1.

Conclusions

Circulating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo’s involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS.
(+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease
Authors: Longhitano Lucia , Distefano Alfio , Musso Nicolò , Bonacci Paolo , Orlando Laura , Giallongo Sebastiano , Tibullo Daniele , Denaro Simona , Lazzarino Giuseppe , Ferrigno Jessica , Nicolosi Anna , Alanazi Amer M. , Salomone Federico , Tropea Emanuela , Barbagallo Ignazio Alberto , Bramanti Vincenzo , Li Volti Giovanni , Lazzarino Giacomo , Torella Daniele , Amorini Angela Maria
Published: January 2024

Background

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles in NAFLD pathogenesis. The unfolded protein response in mitochondria (UPRmt) is an adaptive mechanism that aims to restore mitochondrial protein homeostasis and mitigate cellular stress. This study aimed to investigate the effects of ( +)-Lipoic acid (ALA) on UPRmt, inflammation, and oxidative stress in an in vitro model of NAFLD using HepG2 cells treated with palmitic acid and oleic acid to induce steatosis.

Results

Treatment with palmitic and oleic acids increased UPRmt-related proteins HSP90 and HSP60 (heat shock protein), and decreased CLPP (caseinolytic protease P), indicating ER stress activation. ALA treatment at 1 μM and 5 μM restored UPRmt-related protein levels. PA:OA (palmitic acid:oleic acid)-induced ER stress markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin Protein), and BAX (Bcl-2-associated X protein) were significantly reduced by ALA treatment. ALA also enhanced ER-mediated protein glycosylation and reduced oxidative stress, as evidenced by decreased GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi 1), and GSR (glutathione-disulfide reductase) expression and increased GSH (Glutathione) levels, and improved cellular senescence as shown by the markers β-galactosidase, γH2Ax and Klotho-beta.

Conclusions

In conclusion, ALA ameliorated ER stress, oxidative stress, and inflammation in HepG2 cells treated with palmitic and oleic acids, potentially offering therapeutic benefits for NAFLD providing a possible biochemical mechanism underlying ALA beneficial effects.

Graphical Abstract
Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study
Authors: Sun Dongren , Wang Rui , Du Qin , Zhang Ying , Chen Hongxi , Shi Ziyan , Wang Xiaofei , Zhou Hongyu
Published: January 2024

Background

Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent.

Objective

We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure.

Methods

MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis.

Results

After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (p = .0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw (p = .0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw (p = .0154, beta (se) = − 9.0301 (3.7281)), cuneus THw (p = .0418, beta (se) =  − 0.0020 (0.0010)), lateral orbitofrontal THw (p = .0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw (p = .0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology.

Conclusion

Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.
The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment
Authors: Yin Qinan , Ma Haodi , Dong Yirui , Zhang Shunshun , Wang Junxiang , Liang Jing , Mao Longfei , Zeng Li , Xiong Xin , Chen Xingang , Wang Jingjing , Zheng Xuewei
Published: January 2024

Background

The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches.

Methods

Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated.

Results

A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3.

Conclusions

PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.