bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender-based violence and associated factors among private college female students in Dessie City, Ethiopia: mixed method study
Authors: Gebrie Selamawit , Wasihun Yitbarek , Abegaz Zinet , Kebede Natnael
Published: December 2022

Introduction

Violence against girls and young women, mostly those in educational settings, has been gaining increasing attention. School-based gender-based violence represents a serious obstacle. As a result, it would be a threat to the achievement of the sustainable development goals, strive for gender equality in all our programs, right from the planning stages, to make sure we are as equitable as possible. Little was studied to explore reasons, opinions, and perceptions towards gender-based violence. Also, studies that are conducted on private college female students are limited. Important evidence about underlining reasons for gender-based violence against private college students will be explored. Therefore, to assess the prevalence of gender-based violence and associated factors among Private college female students in Dessie City, Ethiopia, 2021.

Methods

A facility-based mixed method concurrent triangulation study design was conducted among 435 randomly selected Private college female students in Dessie City. Self-administered questionnaire and an in-depth interview were used to collect the data. The collected data were cleaned and entered into Epi data and analyzed using a statistical package for social science. Descriptive statistics were conducted and the results were reported using frequency, and percentile. Binary logistic regression was performed to identify associated factors. Adjusted odds ratios with 95% confidence intervals and p values < 0.05 were used to explain statistically significant associations. Qualitative data were transcribed, translated, and analyzed manually using thematic analysis.

Results

The study showed the prevalence of gender-based violence was 251 (62.6%) (CI 0.512–0.683) Private college female students in Dessie city Administration. age less than 20 years and 20–24 years, [AOR = 0.19, 95% CI (0.03–0.92)] and [AOR = 0.106, 95% CI (0.02–0.44)], tight family control, [AOR = 6.14, 95% CI (1.38–7.1)], family discussion on RH and related personal issue [AOR = 0.091, 95% CI (0.03–0.27)], Witnessed father abuse mother at childhood; [AOR = 4.04, 95% CI (1.36–12.1)], had drunkenness female or boyfriend; [AOR = 5.12, 95% CI (1.58–16.5)] had significant association with gender-based violence.

Conclusions

In this study, the high prevalence of gender-based violence among Private college female students is higher as compared to others. This is because the life of young girls is being abandoned as a result of gender-based violence, such as dropout from their education, unwanted pregnancy, abortion, sexually transmitted infections, and psychological disturbance, which decreases the productivity of girls. This is totally against the strategy and consensus of universal education for women and girls and adolescent health stated in the sustainable development goal.
The impact of nurse-led nonpharmacological multidisciplinary holistic nursing care on fatigue patients receiving hemodialysis: a randomized, parallel-group, controlled trial
Authors: Zuo Manhua , Zhu Wensheng , Lin Jinrong , Zhuo Jing , He Xirui , Jing Xinghui , Tang Jun , Deng Renli
Published: December 2022

Background

Fatigue is a symptom characterized by an elevated prevalence in patients undergoing hemodialysis, which may cause extreme mental and muscular debilitation, significantly influencing social interaction, life quality and well-being. However, the significance of fatigue to patients undergoing hemodialysis has not been recognized yet, and prevention and management of fatigue in this population have not been thoroughly investigated. Additionally, previous studies mainly focused on muscular fatigue, while mental fatigue has been seldom discussed. This study aims to investigate the interaction between nurses and multidisciplinary of nonpharmacological integrated care interventions (NICIs) and assess the impact of fatigue on patients undergoing hemodialysis.

Methods

The integrative nonpharmacological care interventions in this study included walking, motivational interviewing (MI) and health education regarding behavioral self-management. A single-center randomized controlled trial was conducted in the dialysis center of the nephrological department in a tertiary affiliated hospital of medical university from January to June 2019. A total of 118 patients were selected and randomly divided into the intervention group (IG) and the control group (CG). Four patients dropped out during the study, and 114 patients were enrolled for the eventual analysis. The 60 patients in the IG received routine nursing combined with integrated care interventions, while the 54 patients in the CG received routine nursing only. This study lasted for six months.

Results

The experimental group exhibited significant reductions of overall fatigue (2.26 vs. 0.48), mental fatigue (1.41 vs. 0.54), muscular fatigue (2.13 vs. 0.75), and some biochemical indicators (e.g., serum urea) (P<0.05), compared with the CG.

Conclusions

Nurses and multidisciplinary teams have been demonstrated to play a key role and interplay function in chronic disease management. Hence, the nurse-led multidisciplinary NICIs significantly alleviated total fatigue (muscular fatigue and mental fatigue) and improved other parameters.

Trial registration

ChiCTR-IOR-16008621 (March 18, 2016)
Knowledge and skills of pre-eclampsia management among healthcare providers working in antenatal clinics in Zanzibar
Authors: Seif Saada Ali , Rashid Salma Ali
Published: December 2022

Background

Pre-eclampsia and eclampsia are the leading causes of perinatal morbidity and mortality worldwide. Early detection and treatment of preeclampsia is lifesaving; however, evidence suggests that the majority of women in low and middle income-countries are not routinely screened for high blood pressure during antenatal care, that those with severe and mild pre-eclampsia are not monitored for blood pressure and proteinuria as needed, and the magnesium sulphate is not administered as needed. The purpose of this study was therefore to assess knowledge and skills in pre-eclampsia and eclampsia management and their associated factors among healthcare providers working in antenatal clinics in Zanzibar.

Methods

This was a cross-sectional analytical study conducted in all levels of healthcare facilities in Zanzibar. The study involved 176 healthcare providers (nurses and doctors) who were randomly selected. A self-administered questionnaire was used to collect data and descriptive and inferential statistics were used in the analysis whereby logistic regression models were employed. The Chi-square coefficient, odds ratio, and 95% confidence intervals were reported, and the level of significance was set at p < 0.05.

Results

The mean age of healthcare providers was 35.94 (SD ± 7.83) years. The proportion of healthcare providers with adequate knowledge was 49.0%, and 47% had adequate skills. Knowledge level was predicted by working in higher healthcare facility levels (AOR: 3.28, 95% CI: 1.29–8.29), and having attended on-the-job training on pre-eclampsia (AOR: 7.8, 95% CI: 2.74 − 22.75). Skills were predicted by having attended on-job training (AOR: 8.6, 95% CI: 2.45 − 30.16), having working experience of five years or above in antenatal care units (AOR: 27.89, 95% CI: 5.28 − 148.89) and being a medical doctor or assistant medical doctor (AOR: 18.9, 95% CI: 2.1–166).

Conclusion

Approximately half of Zanzibar’s ANC healthcare workers demonstrated inadequate knowledge and skills in preeclampsia care, indicating a critical need for targeted interventions to reduce maternal morbidity and mortality. Knowledge is predicted by attending on-the-job training and working in higher healthcare facility level, while skills is predicted by attending on job training, more years of working experience in antenatal care units and being a medical doctor or assistant medical doctor The study recommends the healthcare facility institutions to provide on-the-job training to for the healthcare providers working in lower healthcare facility levels.
Effects of garlic and lemon essential oils on performance, digestibility, plasma metabolite, and intestinal health in broilers under environmental heat stress
Authors: Elbaz Ahmed M. , Ashmawy Eman S. , Salama Atif A. , Abdel-Moneim Abdel-Moneim Eid , Badri Faisal B. , Thabet Hany A.
Published: December 2022

Background

Natural feed additives play an important role in poultry production due to their safety and potential properties as an antioxidant and antimicrobial, as well as a growth stimulant. The present research was designed to assess the influence of dietary supplementation of either garlic, lemon essential oil, or their mixture on performance, nutrient digestibility, plasma constituents, immunity, and oxidative status, as well as intestinal development assessed by microbiota—histomorphology development in broilers under environmental heat stress.

Methods

A total of 480 broiler chicks (Ross 308) at one-day-old were randomly divided into four groups (120 chicks/ group). The control group received the basal diet (CON), while the other three groups received the basal diet supplemented with 200 mg/kg garlic essential oil (GEO), 200 mg/kg lemon essential oil (LEO), and their mixture (GLO) 200 mg/kg diet, respectively for 35 days.

Results

The obtained results revealed that broilers fed essential oils as a mixture or individually had an improvement in average body weight, feed conversion ratio, carcass dressing, and an increase in digestive enzymes activities compared to the control group, furthermore, there was a reduction in the mortality rate and abdominal fat content. Adding essential oils as a mixture or individually led to a decrease in (P < 0.05) blood plasma triglycerides, cholesterol, low-density lipoprotein, and an increase in high-density lipoprotein. Broilers fed diets supplemented with essential oils as a mixture or individually had higher values of superoxide dismutase and glutathione peroxidase; while plasma malondialdehyde was lower (P < 0.05) compared to the control diet. Moreover, there was a significant enhancement in intestinal microbial content, and intestinal histological status of chickens fed with essential oils.

Conclusions

Conclusively, including the mixture of essential oils improved performance, nutrient digestibility, and digestive enzymes activities. It also enhanced immunity, antioxidant state, and lipid profile, and gut microbiota— histomorphology in broilers. It was proposed that the broilers diet be supplemented with a mixture of essential oils to a mitigation of the effects of heat stress.
A new S. suis serotype 3 infection model in pigs: lack of effect of buprenorphine treatment to reduce distress
Authors: Liedel Carolin , Mayer Leonie , Einspanier Almuth , Völker Iris , Ulrich Reiner , Rieckmann Karoline , Baums Christoph G.
Published: December 2022

Background

Streptoccocus suis (S. suis) is a major porcine pathogen causing meningitis, septicemia, arthritis and endocarditis. These diseases severely impair welfare of pigs. Experimental studies in pigs are important to better understand the pathogenesis and to identify protective antigens, as so far there is no vaccine available protecting against various serotypes (cps). Due to the severity of disease, application of appropriate refinement strategies in experimental S. suis infections is essential to reduce distress imposed on the piglets without jeopardizing the scientific output. The objectives of this study were to evaluate buprenorphine treatment as a refinement measure and serum cortisol levels as a distress read out parameter in a new S. suis cps3 infection model in pigs.

Results

Intravenous application of 2 × 108 CFU of S. suis cps3 (sly+, mrp+) to 6-week-old piglets led to severe morbidity in approximately 50% of the animals. Main pathological findings included suppurative meningoencephalitis and arthritis as well as fibrinosuppurative endocarditis. Buprenorphine treatment (0.05 mg/kg every 8 h) did not prevent signs of severe pain, high clinical scores, moderate to severe pathologies or high levels of serum cortisol in single severely affected piglets. Significant differences in the course of leukocytosis, induction of specific antibodies and bactericidal immunity were not recorded between groups with or w/o buprenorphine treatment. Of note, clinically unobtrusive piglets showed serum cortisol levels at 2 and 5 days post infectionem (dpi) comparable to the levels prior to infection with cps3. Cortisol levels in serum were significantly increased in piglets euthanized due to severe disease in comparison to clinically unobtrusive pigs.

Conclusions

Different clinical courses and pathologies are induced after intravenous challenge of piglets with 2 × 108 CFU of this S. suis cps3 strain. The chosen protocol of buprenorphine application does not prevent severe distress in this infection model. Important parameters of the humoral immune response, such as the level of IgM binding to S. suis cps3, do not appear to be affected by buprenorphine treatment. Serum cortisol is a meaningful parameter to measure distress in piglets experimentally infected with S. suis and to evaluate refinement strategies. In this intravenous model, which includes close clinical monitoring and different humane endpoints, clinics and cortisol levels suggest convalescence in surviving piglets within 5 days following experimental infection.
Transcriptome analysis of PK-15 cells expressing CSFV NS4A
Authors: Lv Huifang , Peng Zhifeng , Jia Bingxin , Jing Huiyuan , Cao Sufang , Xu Zhikun , Dong Wang
Published: December 2022

Background

Classical swine fever (CSF) is a severe disease of pigs that results in huge economic losses worldwide and is caused by classical swine fever virus (CSFV). CSFV nonstructural protein 4 A (NS4A) plays a crucial role in infectious CSFV particle formation. However, the function of NS4A during CSFV infection is not well understood. 

Results

In this study, we used RNA-seq to investigate the functional role of CSFV NS4A in PK-15 cells. A total of 3893 differentially expressed genes (DEGs) were identified in PK-15 cells expressing NS4A compared to cells expressing the empty vector (NC). Twelve DEGs were selected and further verified by RT‒qPCR. GO and KEGG enrichment analyses revealed that these DEGs were associated with multiple biological functions, including cell adhesion, apoptosis, host defence response, the inflammatory response, the immune response, and autophagy. Interestingly, some genes associated with host immune defence and inflammatory response were downregulated, and some genes associated with host apoptosis and autophagy were upregulated.

Conclusion

CSFV NS4A inhibits the innate immune response, and suppresses the expression of important genes associated with defence response to viruses and inflammatory response, and regulates cell adhesion, apoptosis and autophagy.
Negative regulation of interferon regulatory factor 6 (IRF6) in interferon and NF-κB signalling pathways of common carp (Cyprinus carpio L.)
Authors: Liang Yaxin , Liu Rongrong , Zhang Jiahui , Chen Yixin , Shan Shijuan , Zhu Yaoyao , Yang Guiwen , Li Hua
Published: December 2022

Background

Interferon (IFN) regulatory factors (IRFs) is a kind of transcription factors, which play an important role in regulating the expression of type I IFN and related genes. In mammals, IRF6 is not relevant with IFN expression, while zebrafish IRF6 was reported to be a positive regulator of IFN expression and could be phosphorylated by both MyD88 and TBK1. However, the role of IRF6 in the immune response and IFN transcription of common carp is unknown.

Results

In the present study, the cDNA of IRF6 gene (CcIRF6) was cloned from common carp using RACE technique, with a total length of 1905 bp, encoding 471 amino acid residues, which possesses two functional domains of DBD and IAD. Similarity analysis showed that CcIRF6 had more than 50% similarity with IRFs of other vertebrates, and had the highest similarity with grass carp and zebrafish, among which the DBD domain was much more conserved. The phylogenetic analysis showed that CcIRF6 is in the branch of Osteichthyes and has the closest relationship with grass carp. In healthy common carp, the CcIRF6 was expressed in all the examined tissues, with the highest level in the oral epithelium, and the lowest level in the head kidney. After intraperitoneal injection of poly(I:C) or Aeromonas hydrophila, the expression of CcIRF6 increased in spleen, head kidney, foregut and hindgut of common carp. Moreover, poly(I:C), LPS, PGN and flagellin induced the expression of CcIRF6 in peripheral leukocytes and head kidney leukocytes of common carp in vitro. In EPC cells, CcIRF6 inhibited the expression of some IFN-related genes and pro-inflammatory cytokines, and dual luciferase reporter assay showed that CcIRF6 reduced the activity of IFN and NF-κB reporter genes.

Conclusions

The present study suggests that CcIRF6 is involved in the antiviral and antibacterial immune response of common carp, and negatively regulate the expression of IFN and NF-κB signalling pathways, which provides a theoretical basis for the study and prevention of fish disease pathogenesis.
Strategic optimization of conditions for the solubilization of GST-tagged amphipathic helix-containing ciliary proteins overexpressed as inclusion bodies in E. coli
Authors: Shendge Amruta A. , D’Souza Jacinta S.
Published: December 2022

Expression of affinity-tagged recombinant proteins for crystallography, protein–protein interaction, antibody generation, therapeutic applications, etc. mandates the generation of high-yield soluble proteins. Although recent developments suggest the use of yeast, insect, and mammalian cell lines as protein expression platforms, Escherichia coli is still the most popular, due mainly to its ease of growth, feasibility in genetic manipulation and economy. However, some proteins have a spontaneous tendency to form inclusion bodies (IBs) when over-expressed in bacterial expression systems such as E. coli, thus posing a challenge in purification and yield. At times, small peptides undergo degradation during protein production and hence using suitable tags could circumvent the problem. Although several independent techniques have been used to solubilize IBs, these cannot always be applied in a generic sense. Although tagging a GST moiety is known to enhance the solubility of fusion proteins in E. coli, resulting in yields of 10–50 mg/L of the culture, the inherent nature of the protein sequence at times could lead to the formation of IBs. We have been working on a Myc Binding Protein-1 orthologue, viz. Flagellar Associated Protein 174 (FAP174) from the axoneme of Chlamydomonas reinhardtii that binds to an A-Kinase Anchoring Protein 240 (AKAP240) which has been annotated as Flagellar Associated Protein 65 (FAP65). Using an in-silico approach, we have identified two amphipathic helices on FAP65 (CrFAP65AH1 and CrFAP65AH2) that are predicted to bind to FAP174. To test this prediction, we have cloned the GST-tagged peptides, and overexpressed them in E. coli that have resulted in insoluble IBs. The yields of these over-expressed recombinant proteins dropped considerably due to IB formation, indicating aggregation. An integrated approach has been used to solubilize four highly hydrophobic polypeptides, viz. two amphipathic helices and the respective proline variants of FAP65. For solubilizing these polypeptides, variables such as non-denaturing detergents (IGEPAL CA-630), changing the ionic strength of the cell lysis and solubilization buffer, addition of BugBuster®, diluting the cell lysate and sonication were introduced. Our statistically viable results yielded highly soluble and functional polypeptides, indiscreet secondary structures, and a yield of ~ 20 mg/L of the E. coli culture. Our combinatorial strategy using chemical and physical methods to solubilize IBs could prove useful for hydrophobic peptides and proteins with amphipathic helices.
Transcriptome-phenotype matching analysis of how nitrogen sources influence Lacticaseibacillus rhamnosus tolerance to heat stress and oxidative stress
Authors: Zhang Chenchen , Cheng Haohao , Han Yuemei , Wa Yunchao , Chen Dawei , Guan Chengran , Huang Yujun , Gu Ruixia
Published: December 2022

Background

Spray drying is the most cost-effective production method for lactic acid bacteria starters, but heat and oxidative stresses result in low survival rates. The heat stress and oxidative stress tolerance of Lacticaseibacillus rhamnosus cultured in tryptone-free MRS (NP-MRS) broth was much stronger than that in MRS or tryptone-free MRS broth supplemented with phenylalanine (Phe-MRS). Here, multiple transcriptome-phenotype matching was performed on cells cultured in NP-MRS, MRS and Phe-MRS broths to reveal the mechanism by which nitrogen sources influence L. rhamnosus tolerance to heat stress and oxidative stress.

Results

Compared with cells cultured in NP-MRS broth, 83 overlapping differentially expressed genes (DEGs) were downregulated by either tryptone or phenylalanine. The overlapping DEGs were mainly classified into carbohydrate metabolism and membrane transport pathways, which are often repressed by glucose during carbon catabolite repression (CCR). In the presence of glucose, the heat stress or oxidative stress tolerance of L. rhamnosus hsryfm 1301 was not strengthened by supplementation with secondary carbohydrates. Replacing glucose with mannose, fructose or ribose improved the heat stress and oxidative stress tolerance of L. rhamnosus hsryfm 1301 (5 to 46-fold).

Conclusions

Alleviation of CCR might be a reason for the resistance of L. rhamnosus hsryfm 1301 to heat stress and oxidative stress in a low-nitrogen environment. The survival rate of L. rhamnosus during spray drying will hopefully be improved by relieving CCR. It is a new discovery that nitrogen sources influence CCR in L. rhamnosus.
Regulation of mitochondrial complex III activity and assembly by TRAP1 in cancer cells
Authors: Matassa Danilo Swann , Criscuolo Daniela , Avolio Rosario , Agliarulo Ilenia , Sarnataro Daniela , Pacelli Consiglia , Scrima Rosella , Colamatteo Alessandra , Matarese Giuseppe , Capitanio Nazzareno , Landriscina Matteo , Esposito Franca
Published: December 2022

Background

Metabolic reprogramming is an important issue in tumor biology. A recently-identified actor in this regard is the molecular chaperone TRAP1, that is considered an oncogene in several cancers for its high expression but an oncosuppressor in others with predominant oxidative metabolism. TRAP1 is mainly localized in mitochondria, where it interacts with respiratory complexes, although alternative localizations have been described, particularly on the endoplasmic reticulum, where it interacts with the translational machinery with relevant roles in protein synthesis regulation.

Results

Herein we show that, inside mitochondria, TRAP1 binds the complex III core component UQCRC2 and regulates complex III activity. This decreases respiration rate during basal conditions but allows sustained oxidative phosphorylation when glucose is limiting, a condition in which the direct TRAP1-UQCRC2 binding is disrupted, but not TRAP1-complex III binding. Interestingly, several complex III components and assembly factors show an inverse correlation with survival and response to platinum-based therapy in high grade serous ovarian cancers, where TRAP1 inversely correlates with stage and grade and directly correlates with survival. Accordingly, drug-resistant ovarian cancer cells show high levels of complex III components and high sensitivity to complex III inhibitory drug antimycin A.

Conclusions

These results shed new light on the molecular mechanisms involved in TRAP1-dependent regulation of cancer cell metabolism and point out a potential novel target for metabolic therapy in ovarian cancer.
Systemic drug-related intertriginous and flexural exanthema-like eruption after Oxford-AstraZeneca COVID-19 vaccine
Authors: Di Bona Danilo , Miniello Andrea , Nettis Eustachio
Published: December 2022

Systemic drug-related intertriginous and flexural exanthema (SDRIFE) is an adverse drug reaction which manifests as a symmetrical erythematous rash involving the skin folds after systemic drug exposure. A vast array of possible side effects associated with administration of different anti-SARS-CoV-2 vaccines have been reported in literature since the beginning of the COVID-19 pandemic, but only few times SDRIFE-like eruptions have been described in this context. We discuss here a case of SDRIFE-like eruption following the second dose of Oxford-Astrazeneca Vaxzevria vaccine.
Harnessing bioactive nanomaterials in modulating tumor glycolysis-associated metabolism
Authors: Gu Zhengying , Yu Chengzhong
Published: December 2022

Glycolytic reprogramming is emerging as a hallmark of various cancers and a promising therapeutic target. Nanotechnology is revolutionizing the anti-tumor therapeutic approaches associated with glycolysis. Finely controlled chemical composition and nanostructure provide nanomaterials unique advantages, enabling an excellent platform for integrated drug delivery, biochemical modulation and combination therapy. Recent studies have shown promising potential of nanotherapeutic strategies in modulating tumor glycolytic metabolism alone or in combination with other treatments such as chemotherapy, radiotherapy and immunotherapy. To foster more innovation in this cutting-edge and interdisciplinary field, this review summarizes recent understandings of the origin and development of tumor glycolysis, then provides the latest advances in how nanomaterials modulate tumor glycolysis-related metabolism. The interplay of nanochemistry, metabolism and immunity is highlighted. Ultimately, the challenges and opportunities are presented.
Incidence and severity of immune-related hepatitis after dual checkpoint therapy is linked to younger age independent of herpes virus immunity
Authors: Zhang Zhen , Rafei-Shamsabadi David , Lehr Saskia , Buettner Nico , Diehl Rebecca , Huzly Daniela , Pinato David J , Thimme Robert , Meiss Frank , Bengsch Bertram
Published: December 2022

Background and Aims

Dual immune checkpoint blockade (ICB) therapy can result in immune-related-adverse events (irAE) such as ICB-hepatitis. An expansion of effector-memory (TEM) CD4 T cells associated with antiviral immunity against herpesviridae was implicated in ICB-hepatitis. Notably, these memory subsets are frequently associated with age. Here, we sought to understand baseline patient, immune and viral biomarkers associated with the development of ICB-hepatitis to identify currently lacking baseline predictors and test if an expansion of TEM or positive serology against herpesviridae can predict ICB-hepatitis.

Methods

A discovery (n = 39) and validation cohort (n = 67) of patients with advanced melanoma undergoing anti-PD-1&anti-CTLA4 combination therapy (total n = 106) were analyzed for baseline clinical characteristics, occurrence of irAE and oncological outcomes alongside serological status for CMV, EBV and HSV. Immune populations were profiled by high-parametric flow cytometry (n = 29).

Results

ICB-hepatitis occurred in 59% of patients within 100 days; 35.9% developed severe (CTCAE 3–4) hepatitis. Incidence of ICB-hepatitis was higher in the younger (< 55y: 85.7%) compared to older (> = 55y: 27.8%) age group (p = 0.0003), occured earlier in younger patients (p < 0.0001). The association of younger age with ICB-Hepatitis was also observed in the validation cohort (p = 0.0486). Incidence of ICB-hepatitis was also associated with additional non-hepatic irAE (p = 0.018), but neither positive IgG serostatus for CMV, EBV or HSV nor TEM subsets despite an association of T cell subsets with age.

Conclusion

Younger age more accurately predicts ICB-hepatitis after anti-PD-1&anti-CTLA4 checkpoint therapy at baseline compared to herpes virus serology or TEM subsets. Younger patients should be carefully monitored for the development of ICB-hepatitis.
Disruption of C/EBPβ-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain
Authors: Wu Dan , Zhang Yanqiong , Zhao Chunhui , Li Qiuyue , Zhang Junhong , Han Jiaxin , Xu Zhijian , Li Junfang , Ma Yan , Wang Ping , Xu Haiyu
Published: December 2022

Background

Growing evidence shows that C-Type Lectin Domain Containing 7A (Clec7a) may be involved into neuroinflammatory injury of various neurological diseases. However, its roles in neuropathic pain remain unclear.

Methods

A chronic constriction injury (CCI) rat model was constructed, and gene expression profilings in spinal cord tissues of CCI-insulted rats were detected by both microarray and RNA-seq studies. A series of bioinformatics analyses identified C/EBPβ-Clec7a to be a candidate axis involved into neuropathic pain. Then, its roles in mechanical allodynia, and pathological and molecular changes during CCI progression were determined by various gain-of-function and loss-of-function experiments in vivo and in vitro.

Results

Significant upregulation of Clec7a at both mRNA and protein levels were verified in spinal cord tissues of CCI-insulted rats. Clec7a knockdown markedly attenuated CCI-induced mechanical allodynia, obstructed Syk, ERK and JNK phosphorylation, inhibited NLRP3 inflammasome and caspase-1 activation, GSDMD cleavage, and consequently reduced the release of pro-inflammatory cytokines (all P < 0.05). Mechanically, the rat Clec7a promoter was predicted to bind with transcription factor C/EBPβ, confirmed by Luciferase assay and ChIP-qPCR. Both in vivo and in vitro assays demonstrated that C/EBPβ knockdown significantly suppressed CCI- or LPS/ATP-induced Clec7a upregulation, and subsequently reduced Syk, ERK and JNK phosphorylation, NLRP3 oligomerization, caspase-1 activation, GSDMD expression and pyroptosis, which were markedly reversed by the co-transfection of Clec7a expression vector.

Conclusions

This pre-clinical investigation reveals that C/EBPβ-Clec7a axis may be a potential target for relieving neuropathic pain through alleviating neuroinflammation, paving its way for clinical translation as a promising approach for neuropathic pain therapy.
The role of the oral microbiome in smoking-related cardiovascular risk: a review of the literature exploring mechanisms and pathways
Authors: Maki Katherine A. , Ganesan Sukirth M. , Meeks Brianna , Farmer Nicole , Kazmi Narjis , Barb Jennifer J. , Joseph Paule V. , Wallen Gwenyth R.
Published: December 2022

Cardiovascular disease is a leading cause of morbidity and mortality. Oral health is associated with smoking and cardiovascular outcomes, but there are gaps in knowledge of many mechanisms connecting smoking to cardiovascular risk. Therefore, the aim of this review is to synthesize literature on smoking and the oral microbiome, and smoking and cardiovascular risk/disease, respectively. A secondary aim is to identify common associations between the oral microbiome and cardiovascular risk/disease to smoking, respectively, to identify potential shared oral microbiome-associated mechanisms. We identified several oral bacteria across varying studies that were associated with smoking. Atopobium, Gemella, Megasphaera, Mycoplasma, Porphyromonas, Prevotella, Rothia, Treponema, and Veillonella were increased, while Bergeyella, Haemophilus, Lautropia, and Neisseria were decreased in the oral microbiome of smokers versus non-smokers. Several bacteria that were increased in the oral microbiome of smokers were also positively associated with cardiovascular outcomes including Porphyromonas, Prevotella, Treponema, and Veillonella. We review possible mechanisms that may link the oral microbiome to smoking and cardiovascular risk including inflammation, modulation of amino acids and lipids, and nitric oxide modulation. Our hope is this review will inform future research targeting the microbiome and smoking-related cardiovascular disease so possible microbial targets for cardiovascular risk reduction can be identified.
Calcitriol increases MBNL1 expression and alleviates myotonic dystrophy phenotypes in HSALR mouse models
Authors: Huang Kun , Wang Dan-Dan , Hu Wen-Bao , Zeng Wei-Qian , Xu Xia , Li Qiu-Xiang , Bi Fang-Fang , Yang Huan , Qiu Jian
Published: December 2022

Background

Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3′ untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1.

Methods

All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice.

Results

In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells.

Conclusion

Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.
Targeting macrophages: a novel treatment strategy in solid tumors
Authors: Liu Mengmeng , Liu Lina , Song Yongping , Li Wei , Xu Linping
Published: December 2022

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.
Exposure to violence is associated with decreased neural connectivity in emotion regulation and cognitive control, but not working memory, networks after accounting for socioeconomic status: a preliminary study
Authors: Mattheiss Samantha R. , Levinson Hillary , Rosenberg-Lee Miriam , Graves William W.
Published: December 2022

Previous research has demonstrated behavioral and neural differences associated with experiencing adversity. However, adversity is unlikely to be a monolithic construct, and we expect that examining effects of more specific components such as exposure to violence in the home community will yield more concretely interpretable results. Here we account for effects of low socioeconomic status (SES) to examine the specific effects of exposure to violence on functional connectivity between brain areas known to be related to emotion regulation and working memory. Decreased resting state functional connectivity for individuals exposed to high compared to low levels of violence during childhood was predicted for two sets of areas: (1) bilateral amygdala with anterior medial regions involved in cognitive control of emotion, and (2) the right dorsolateral prefrontal cortex (dlPFC) with frontal and parietal regions implicated in working memory. Consistent with our predictions, increasing exposure to violence was related to decreased resting state functional connectivity between the right amygdala and anterior cingulate cortex, even after accounting for SES. Also after accounting for SES, exposure to violence was related to reductions in connectivity between the right dlPFC and frontal regions, but not with parietal regions typically associated with working memory. Overall, this pattern suggests increased exposure to violence in childhood is associated with reduced connectivity among key areas of the circuitry involved in emotion regulation and cognitive control, but not working memory. These results offer insight into the neural underpinnings of behavioral outcomes associated with exposure to violence, laying the foundation for ultimately designing interventions to address the effects of such exposure.
Occupational safety practice among metal workers in Bangladesh: a community-level study
Authors: Islam Farhin , Alam MR , Mamun SM Abdullah AL , Hossain Mohammad Sorowar
Published: December 2022

Background

The overall information on occupational health and safety (OHS)-related knowledge and workplace practices are scarce in Bangladesh. This study aimed to (i) examine the prevalence of occupational injuries, (ii) explore the level of OHS-related knowledge and practice among workers and associated factors, and (iii) investigate the socioeconomic factors and OHS-related knowledge and practice scores as determinants of injury among metal workers at a community setting in Bangladesh.

Methods

This was a cross-sectional study conducted on all the functional metal workshops in a community of a town. The sociodemographic characteristics, history of injury and its consequences, and the state of knowledge and practice were measured using descriptive statistics. Univariate and multivariate analyses were used to measure the association between practice scores and sociodemographic factors and knowledge. Logistic regression was conducted to get the odds ratio of getting injured.

Results

A high annual rate (82.9%) of occupational injuries was documented in a one-year timeframe and the majority (81.1%) of injured workers lost more than three working days (median 20 days). Workers working in workshops with more than three workers were 3.3 times more likely to be injured [AOR = 3.33, 95% CI = 1.16, 9.58] compared to the workers in factories with one to three workers. Most of the workers had the basic knowledge related to OHS but the mean practice score was very low, 1.86 (SD 1.17). Higher education, lower monthly family income, and being an owner significantly led to higher practice scores.

Conclusions

The OHS-related knowledge was not properly translated into good workplace practices in small informal metal workshops because of the absence of implementation of OHS policies and monitoring by the relevant authority. Government should support the informal metal working sector to increase awareness and skills for the prevention and proper management of injuries and risks, and to ensure access to safety equipment and a safe environment.
A simple and robust method for isolating and analyzing chromatin-bound RNAs in Arabidopsis
Authors: Zhang Qiqi , Zhao Fengli , Wu Zhe , Zhu Danling
Published: December 2022

Background

Chromatin-bound RNAs are the primary product of transcription that undergo on-chromatin processing such as capping, splicing, and polyadenylation. These processing steps then determine the fate of RNAs. Albeit its vital importance, a simple and robust method for isolating different fractions of chromatin-bound RNAs is missing in plants.

Result

Here, we describe our updated method and the associated step-by-step protocol for chromatin-bound RNAs isolation in A. thaliana. The chromatin-bound RNAs isolation is based on the 1 M UREA wash that removes the majority of non-chromatin-associated proteins from the nucleus, as previously developed in mammalian cells. On-demand, the isolated chromatin-bound RNAs can be either used directly for gene-specific analysis or subject to further rRNA removal and also the optional polyadenylated RNA removal, followed by high-throughput sequencing. Detailed protocols for these procedures are also provided. Comparison of sequencing results of chromatin-bound RNAs with and without polyadenylated RNA removal revealed that a small fraction of CB-RNAs is polyadenylated but not yet fully spliced, representing RNA-processing intermediate on-chromatin.

Conclusion

This optimized chromatin-bound RNAs purification method is simple and robust and can be used to study transcription and its-coupled RNA processing in plants.
School-based harm reduction with adolescents: a pilot study
Authors: Fischer Nina Rose
Published: December 2022

A pilot study of Safety First: Real Drug Education for Teens showed significant results pre to post curriculum with high school freshmen. Negative outcomes of drug education are linked to a failure to engage students because of developmentally inappropriate materials that include activities that have no relevance to real experiences of young people. The few harm reduction studies showed increased student drug related knowledge. Students were less likely to consume substances, and less likely to consume to harmful levels. More studies are necessary to evidence harm reduction efficacy in the classroom. The goal of this study was to measure harm reduction knowledge and behaviors, including drug policy advocacy, before and after Safety First. Data were analyzed using McNemar’s test, ANOVA, linear regression,t-tests and thematic coding. Survey results, corroborated by the qualitative findings, showed a significant increase (p < .05) in high school freshmen harm reduction knowledge and behaviors in relationship to substance use pre to post Safety First. This increase related to a decrease in overall substance use. Harm reduction is often perceived as a controversial approach to substance use. These findings have implications for further study of what could be a promising harm reduction-based substance use intervention with teens.
Clinical and sonographic improvement of developmental dysplasia of the hip: analysis of 948 patients
Authors: Bakti Karim , Lankinen Vilma , Helminen Mika , Välipakka Jarmo , Laivuori Hannele , Hyvärinen Anna
Published: December 2022

Background

Developmental dysplasia of the hip is a common condition, which varies in severity. Abduction treatment is widely used to correct the development of the hips, but mild forms of DDH can also recover spontaneously. The purpose of this study was to evaluate factors affecting the rate of improvement of developmental dysplasia of the hip, and evaluate any risk factors slowing the process.

Material and methods

The study population consisted of patients diagnosed with DDH in Tampere University hospital in the years 1998–2018. Data were retrospectively collected, and associations between clinical variables and rate of improvement were analyzed. Alpha angles were assessed monthly, and associations between risk factors and improvement of alpha angles were studied. A total of 948 patients were included in the analysis.

Results

More severe first status of the hips was associated with faster improvement in dynamic ultrasound compared to milder DDH in univariate design in first 3 months of age; in the multivariable design, Ortolani positivity was conversely associated with lower alpha angles in 1-month follow-up. Immediate abduction treatment was associated with faster recovery rate compared to delayed abduction or watchful waiting. Female sex and positive family history were associated with slower rate of improvement and lower alpha angles. In multivariable design, female sex, positive family history and treatment strategy remained statistically significant as initiation time of the treatment explained the first found association of clinical hip status and the recovery rate after 2 months of age.

Conclusion

Female sex and positive family history might be independent risk factors for slower recovery in DDH before 6 months of age. These children might need special attention in their follow-up plans and abduction treatment.
Semisynthetic aurones A14 protects against T-cell acute lymphoblastic leukemia via suppressing proliferation and inducing cell cycle arrest with apoptosis
Authors: Wang Meng , Li Lisi , Fan Tengyun , Cao Lixue , Zhang Jiayi , Li Shuang , Liu Chunming , Liu Xifu
Published: December 2022

Background

Acute lymphoblastic leukemia is an aggressive neoplasm and seriously threatens human health. A14 is one kind of semisynthetic aurone that exhibits the capability to inhibit prostate cancer, but little is known about the role of A14 on T-cell acute lymphoblastic leukemia.

Methods

Firstly, the effects of A14 on the ability of leukemia cells to proliferate were measured by Vi-cell counter. Then, we detected the cell cycle and apoptosis by flow cytometry and characterized the related protein expression using immunoblotting. In addition, we constructed stable luciferase expressing cell lines for use in a cell derived xenograft mouse model to measure the effect of A14 on T-cell acute lymphoblastic leukemia.

Results

Results exhibited that A14 markedly suppressed cell proliferation and induced G2/M phase arrest along with cell cycles regulating proteins changes. A14 led to apoptosis in leukemia cells, at least partly, through the cytochrome c signaling pathway. Experiments in cell derived xenograft mouse model also showed that A14 markedly ameliorated the survival rate.

Conclusions

The present study revealed that semisynthetic aurones A14 can effectively protect against T-cell acute lymphoblastic leukemia progression both in vitro and in vivo, indicating the capability of A14 as a promising drug for the treatment of T-cell acute lymphoblastic leukemia.