Schistosoma japonicum infection-mediated downregulation of lncRNA Malat1 contributes to schistosomiasis hepatic fibrosis by the Malat1/miR-96/Smad7 pathway.

BACKGROUND: Schistosoma japonicum infection causes hepatic fibrosis, a primary cause of morbidity and mortality associated with the disease, and effective treatments are still lacking. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenic process of various tissue fibroses. However, the role of lncRNAs in schistosomiasis hepatic fibrosis (HF) is poorly understood. Understanding the role of lncRNAs in schistosomiasis HF will enhance knowledge of disease processes and aid in the discovery of therapeutic targets and diagnostic biomarkers. METHODS: Differentially expressed lncRNA profiles in primary hepatic stellate cells (HSCs) of mice infected with S. japonicum were identified using high-throughput lncRNA sequencing. Primary HSCs were isolated from infected mice using collagenase digestion and density-gradient centrifugation, cultured in DMEM with 10% fetal bovine serum. Dual-luciferase reporter assays, nuclear cytoplasm fractionation and RIP assays were employed to assess the relationship between Malat1 and miRNA-96. Malat1 lentivirus and ASO-Malat1 were constructed for forced expression and downregulated expression of Malat1. The Malat1-KO mouse was constructed by CRISPR/Cas9 technology. Pathological features of the liver were evaluated by hematoxylin-eosin (HE), Masson's trichrome staining and immunohistochemistry (IHC). The expression levels of fibrosis-related genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot. RESULTS: A total of 1561 differentially expressed lncRNAs were identified between infected and uninfected primary HSCs. Among the top altered lncRNAs, the downregulated Malat1 was observed in infected HSCs and verified by qPCR. Treatment of infected mice with praziquantel (PZQ) significantly increased the Malat1 expression. Elevated Malat1 expression in infected primary HSC reduced the expressions of profibrogenic genes, whereas Malat1 knockdown had the opposite effect. Moreover, Malat1 was found to interact with miR-96, a profibrotic miRNA, by targeting Smad7. Forced Malat1 expression reduced miR-96 levels in infected primary HSCs, attenuating fibrogenesis and showing negative correlation between Malat1 expression and the expression levels of miR-96 and profibrogenic genes α-SMA and Col1α1. Notably, in Malat1-KO mice, knockout of Malat1 aggravates schistosomiasis HF, while restored Malat1 expression in the infected HSCs reduced the expression of profibrogenic genes. CONCLUSIONS: We demonstrate that lncRNA is involved in regulation of schistosomiasis HF. Elevated lncRNA Malat1 expression in infected HSCs reduces fibrosis via the Malat1/miR-96/Smad7 pathway, thus providing a novel therapeutic target for schistosomiasis HF. Furthermore, Malat1 expression is sensitive to PZQ treatment, thus offering a potential biomarker for assessing the response to chemotherapy.

Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology. Methods: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD. Results: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including ß-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance. Conclusion: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.

The Association Between the Non-essential Metal Mixture and Handgrip Strength in Chinese Community-Dwelling Older Adults.

There is limited research on the effects of non-essential metal (NEM) mixture on handgrip strength in the elderly. This study aimed to assess the associations of single NEMs and their mixture with handgrip strength in Chinese community-dwelling older adults. A total of 3807 elderly people aged 60 years or above were included in this study. Measurement of urinary aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), and gallium (Ga) concentrations was conducted by inductively coupled plasma mass spectrometry (ICP-MS). Handgrip strength was measured using a hand dynamometer. Four statistical models, including general linear regression and generalized additive models (GAMs), as well as Bayesian kernel machine regression (BKMR) and quantile-based computation regression (QGC) models, were used to assess the individual and joint effects of urine NEMs with handgrip strength, respectively. After adjusting for covariates, Ga (ß = - 0.27; 95% CI, - 0.54 ~ - 0.01) and As ( ß  = - 0.34; 95% CI, - 0.61 ~ - 0.07) were negatively associated with handgrip strength. The GAMs and BKMR further suggested that the negative associations of Ga and As with handgrip strength were linear and inverted U-shaped, respectively. The BKMR and QGC models showed that the NEM mixture was negatively related to handgrip strength, with Ga and As contributing the most within the mixture. Moreover, we also observed an interaction between As and Ga on handgrip strength. Longitudinal studies are needed to verify these findings.

Exploring the correlation between innate immune activation of inflammasome and regulation of pyroptosis after intracerebral hemorrhage: From mechanism to treatment.

Stroke has emerged as the primary cause of disability and death globally in recent years. Intracerebral hemorrhage (ICH), a particularly severe kind of stroke, is occurring in an increasing number of people. The two main clinical treatments for ICH now in use are conservative pharmaceutical therapy and surgical intervention, both of which have risks and drawbacks. Consequently, it is crucial to look into the pathophysiology of ICH and consider cutting-edge therapeutic approaches. Recent research has revealed that pyroptosis is a newly identified type of cell death distinguished by the break of the cell membrane and the discharge of pro-inflammatory substances through different routes. Following ICH, glial cells experience pyroptosis, which worsens neuroinflammation. Hence, the onset and progression of ICH are strongly linked to pyroptosis, which is facilitated by different inflammasomes. It is essential to conduct a comprehensive investigation of ICH damage processes and uncover new targets for treatment. The impact and function of pyroptosis in ICH, as well as the activation and regulation of inflammasomes and their mediated pyroptosis pathways will be fully discussed in this review.

Downregulation of Chloride voltage-gated channel 7 contributes to hyperalgesia following spared nerve injury.

Alterations in anion balance potential, along with the involvement of cation-chloride cotransporters, play pivotal roles in the development of hyperalgesia after peripheral nerve injury (PNI). Chloride voltage-gated channel 7 (CLCN7) is the predominant member of the CLC protein family. Investigations on CLCN7 have focused primarily on its involvement in osteosclerosis and lysosomal storage disorders; nevertheless, its contribution to neuropathic pain (NP) has not been determined. In this investigation, we noted high expression of CLCN7 in neurons situated within the spinal dorsal horns (SDHs) and dorsal root ganglions (DRGs). Immunofluorescence analysis revealed that CLCN7 was predominantly distributed among IB4-positive and CGRP-positive neurons. Furthermore, the expression of CLCN7 was observed to be mainly reduced in neurons within the SDHs and in small and medium-sized neurons located in the DRGs of spared nerve injury (SNI) mice. Knockdown of CLCN7 via siRNA in the DRGs resulted in increased mechanical and thermal hyperalgesia in naïve mice. Furthermore, the excitability of cultured DRG neurons in vitro was augmented upon treatment with CLCN7 siRNA. These findings suggested that CLCN7 downregulation following SNI was crucial for the manifestation of mechanical and thermal hyperalgesia, highlighting potential targeting strategies for treating NP.

Association between high-density lipoprotein-related inflammation index and periodontitis: insights from NHANES 2009-2014.

BACKGROUND: Periodontitis, a persistent inflammatory condition, significantly impairs individuals' overall quality of life. Lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), and platelet-to-high-density lipoprotein cholesterol ratio (PHR) are new convenient and economical biomarkers. However, whether the above high-density lipoprotein-related inflammatory biomarkers are associated with periodontitis has rarely been investigated. Therefore, the research endeavor focused on uncovering potential relationships. METHODS: The research encompassed a diverse and extensive sample, comprising 9,470 participants, selected from the National Health and Nutrition Examination Survey spanning the years 2009 to 2014. The association between high-density lipoprotein-related inflammatory biomarkers and periodontitis was explored utilizing a multivariable logistic regression model with weighted analysis. Additionally, the study employed smoothed curve fitting to explore potential nonlinear relationships. Further stratified analyses and interaction tests were performed. RESULTS: This study indicated no apparent association between MHR and PHR with periodontitis, whereas LHR and NHR demonstrated a statistically significant positive relationship with the prevalence of periodontitis. In the fully adjusted model, participants belonging to the highest tertile of both LHR and NHR showed a notably higher likelihood of having periodontitis compared to those in the lowest tertile (LHR: OR = 1.22, 95% CI: 1.06, 1.39; NHR: OR = 1.27, 95% CI: 1.09, 1.49). Furthermore, smooth curve fitting was employed to investigate the potential nonlinear relationship between LHR, NHR, and periodontitis. The results indicated that there was a significant increase in the occurrence of periodontitis when Log2 (LHR) exceeded 1.01 and Log2(NHR) surpassed 2.16 (Log2(LHR): OR = 1.42; 95% CI: 1.19, 1.69; Log2(NHR): OR = 1.40; 95% CI: 1.15, 1.71). The subgroup analysis revealed that the associations between periodontitis and either LHR or NHR, separately, were more pronounced among individuals under the age of 50 and those without hypertension. CONCLUSIONS: This cross-sectional study revealed a positive relationship between LHR、NHR and periodontitis, particularly when these indicators exceeded their thresholds. LHR and NHR may serve as potential inflammatory markers for identifying periodontitis, thereby facilitating early warning for both patients and dentists, and enabling early intervention in the oral environment. Besides, extensive prospective cohort investigations are essential to confirm and solidify this observation.

Identification and mechanistic analysis of neurovascular coupling related biomarkers for diabetic macular edema.

Introduction: Diabetic macular edema (DME) is a major cause of vision loss in the sick with diabetic retinopathy. The occurrence of DME is closely related to the breakdown of neurovascular coupling; however, its underlying mechanism has not been fully elucidated. The aim of this study was to investigate the diagnostic biomarkers and potential molecular mechanisms associated with neurovascular coupling in DME. Methods: The differential expression analysis, STEM, and WGCNA were performed from GSE160306 to identify hub genes. The gene expression was validated by RT-qPCR. The relevant mechanisms of action were investigated through GO, KEGG, and GSEA analyses, as well as co-expression networks. Additionally, the LASSO regression analysis and a nomogram were used to demonstrate the diagnostic effectiveness of the model. Finally, the GenDoma platform was utilized to identify drugs with potential therapeutic effects on DME. Results: Neurotrophic factor receptor (NGFR) was identified as a hub gene related to neurovascular coupling and DME. The expression of NGFR was verified by RT-qPCR in vitro cells. GSEA analysis indicated that high expression of NGFR may affect immunity and inflammatory pathway, thereby regulating neurovascular coupling and mediating the development of DME. The NGFR co-expression network was constructed, which exhibited the correlation with the neurotrophin signaling pathway. Moreover, a diagnostic model for DME based on NGFR and PREX1 demonstrated relatively good diagnostic performance using LASSO regression analysis and the nomogram. And then the GenDoma platform identified drugs with potential therapeutic effects on DME. Conclusion: The high expression of NGFR may lead to abnormal neurovascular coupling and participate in the occurrence of DME by regulating the immunity, inflammatory and neurotrophin signaling pathway. Detection of NGFR and related expression genes may be beneficial for monitoring the occurrence and development of DME.

Rational Construction of Co4(µ-O)6(COO)6 SBU-Based MOFs through Mixed-Ligand Strategy to Enhance Electrocatalytic Oxygen Evolution Performance.

Metal-organic frameworks (MOFs) are increasingly becoming an important choice for developing robust and efficient electrocatalysts; therefore, exploring the relationship between the structure, catalytic activity, and stability of MOFs is of great significance. MOFs 1-3 with different spatial configurations are designed and synthesized based on linear pyridine ligands, tetragonal carboxylic acid ligands, and triangular carboxylic acid ligands, while MOF 4 displays a three-dimensional (3D) supramolecule assembled through a mixed-ligand strategy. Compared with MOFs 1-3, MOF 4 has the lowest overpotential of 106 mV (at 10 mA·cm-2) and a Tafel slope of 80.9 mV·dec-1, as well as sturdy long-term stability in the process of oxygen evolution reaction (OER). The presence of dense metal clusters and µ3-O promotes the optimal catalytic performance of MOF 4. Density functional theory (DFT) calculations of MOF 4 demonstrate that the process from O* to OOH* is the rate-determining step. This investigation further reveals the relationship between MOF structural composition and electrocatalytic OER performance and provides an effective strategy for the assembly of MOF-based electrocatalysts.

Exposure to Multiple Metal(loid)s and Hypertension in Chinese Older Adults.

Evidence about effects of metal(loid)s on hypertension among adults is insufficient. The aim of our study was to evaluate the individual and joint associations between seven selected metal(loid)s and hypertension, including lead (Pb), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), chromium (Cr), and vanadium (V)) in Chinese older adults. This study included 1009 older adults, and the blood concentrations of seven metal(loid)s were evaluated by inductively coupled plasma mass spectrometry (ICP-MS). The following conditions were considered as hypertension: (1) either systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, (2) a self-reported history of hypertension, or (3) currently taking antihypertensive medications. Logistic regression was utilized to investigate the association between individual metal(loid) and hypertension, while Bayesian kernel machine regression (BKMR) was employed to investigate the association of the metal(loid) mixture with hypertension. Adjusted single-metal(loid) model showed a significant positive association between Pb and hypertension (OR = 1.24, 95%CI = 1.03-1.50). This significant association still existed in multi-metal(loid) model (OR = 1.22, 95%CI = 1.01-1.47). BKMR further indicated a positive linear association of Pb with hypertension. The metal(loid) mixture was positively associated with hypertension in older adults, although not significant. Within the mixture, Pb had the highest posterior inclusion probabilities value (PIP = 0.9192). There were multiplicative interactions of Pb and Mn on hypertension. In addition, Pb and Mn had additive effects on the association of other blood metal(loid)s with hypertension. The associations of multiple metal(loid)s with hypertension are dependent on diabetes, areas, age, and BMI. The metal(loid) mixture exposure may contribute to hypertension in Chinese older adults, mainly driven by Pb and interactions of Pb and Mn. Reducing exposure to these metal(loid)s may prevent hypertension among older adults, which is especially true for those living with diabetes.

Factors influencing safe use of drugs among community residents: a cross-sectional study.

BACKGROUND: Researchers have paid little attention to the safety of drug use among community residents (CRs). Irrational use of drugs can lead to health risks. We investigated the situation of knowledge-attitude-practices (KAP) of CRs in Shenzhen (China) for safe use of drugs, and analyzed the main factors influencing drug use. METHODS: A multi-stage, random sampling method was used. We used a validated questionnaire to conduct an online questionnaire survey on the demographic characteristics and KAP of safe use of drugs of CRs in 10 administrative districts of Shenzhen City. The KAP score of safe use of drugs of CRs was analyzed. Influencing factors were identified using a single-factor chi-squared test and binary logistic regression analysis. RESULTS: A total of 7269 valid questionnaires were collected. The average scores of knowledge, attitude, and behavior were (9.08 ± 1.49) (possible range: 0-10), (37.82 ± 3.96) (possible range: 8-40), and (35.82 ± 4.56) (possible range: 8-40), respectively, indicating that they had a better grasp of safe use of drugs. Logistic regression analysis showed that sex, age, education level, occupation, monthly household income per capita, marital status, health status, and different sources of information were the main factors affecting the knowledge and behavior of safe use of drugs of CRs. In addition to the marital status variable, other variables also have a significant impact on attitude towards safe use of drugs of CRs. CONCLUSIONS: Male sex, lower education level, lower income level, average/poor self-rated health status, and single source of drug-use information were the main factors affecting safe use of drugs based on KAP theory. The government and medical workers should carry out various forms of drug-education activities for people with different needs, encourage CRs to learn safe use of drugs, and promote safe use of drugs by CRs through diverse information sources.

Construction and application of "organ-system-centered" undergraduate nursing professional training model.

OBJECTIVE: The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. METHODS: This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. RESULTS: A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. CONCLUSION: The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

Nitrogen enrichment enhances the negative top-down effect on plant functional traits.

Eutrophication resulting from anthropogenic activities has been recognized as a significant driver of changes in ecosystem functioning. Furthermore, it may exacerbate the top-down effect and thus exert an important impact on plant growth. To test this hypothesis, we conducted a 3-year manipulative field experiment to investigate the impacts of nitrogen addition and crab herbivory on the growth of Phragmites australis in the salt marsh of the Yellow River Delta. The results demonstrated that a 3-year nitrogen addition can significantly increase the total nitrogen and carbon content of P. australis leaves, thereby enhancing their nutritional value and palatability, as well as increasing the proportion of leaves consumed by crabs. Therefore, nitrogen addition together with crab herbivory had a significant negative effect on P. australis height, leaf length, and leaf breadth in the ambient crab and procedural crab cage treatment compared to the crab exclusion treatment. The structural equation modeling further substantiated these findings. The model revealed a direct and positive correlation between nitrogen addition and leaf nutrient content (path coefficient = 0.34). Additionally, it demonstrated a direct and positive relationship between leaf nutrient content and the proportion of leaves consumed by crabs (path coefficient = 0.22). Simultaneously, there was an observed negative correlation (path coefficient = - 0.37) between the proportion of leaves consumed by crabs and plant functional traits, represented by leaf length in the model, during 2018. Moreover, the crab exclusion treatment significantly reduced the proportion of leaves consumed by crabs and thus enhanced the P. australis individuals, leaf number, and biomass. Overall, crab herbivory had a significant detrimental top-down effect on the growth of P. australis, and nitrogen enrichment may exacerbate this top-down effect. The findings of our study highlight the combined adverse effects of nutrient enrichment and top-down on plant functional traits and plant growth. The findings of this study will contribute to a comprehensive understanding of the underlying factors influencing vegetation degradation in coastal wetland, thereby establishing a solid theoretical framework for the conservation and management of wetland ecosystems within the context of global environmental change.

Extracellular vesicles for the treatment of ulcerative colitis: A systematic review and meta-analysis of animal studies.

Background: Extracellular vesicles (EVs) are being considered as a potential therapeutic option for ulcerative colitis (UC), and numerous preclinical studies have been conducted on the use of EVs for UC. Methods: A systematic review was conducted to compare the therapeutic effects of mammalian EVs and placebo on UC in animal models, along with a meta-analysis comparing naïve (unmodified) EVs and placebo. The search was performed in four databases (PubMed, Web of Science, Scopus, and EMBASE) up to September 13th, 2023. The primary outcomes included disease activity index (DAI), colonic mucosal damage index (CMDI), and adverse effects (PROSPERO ID: CRD42023458039). Results: A total of 69 studies were included based on pre-determined criteria, involving 1271 animals. Of these studies, 51 measured DAI scores, with 98 % reporting that EVs could reduce DAI scores. Additionally, 5 studies reported CMDI and all showed that EVs could significantly reduce CMDI. However, only 3 studies assessed adverse effects and none reported any significant adverse effects. The meta-analysis of these studies (40 studies involving 1065 animals) revealed that naïve EVs could significantly decrease the DAI score (SMD = -3.00; 95 % CI: -3.52 to -2.48) and CMDI (SMD = -2.10; 95 % CI: -2.85 to -1.35). Conclusion: The results indicate that mammalian EVs have demonstrated therapeutic benefits in animal models of UC; however, the safety profile of EVs remains inadequate which highlights the need for further research on safety outcomes.

PARylation of 14-3-3 proteins controls the virulence of Magnaporthe oryzae.

Magnaporthe oryzae is a devastating fungal pathogen that causes the rice blast disease worldwide. The post-translational modification of ADP-ribosylation holds significant importance in various fundamental biological processes. However, the specific function of this modification in M. oryzae remains unknown. This study revealed that Poly(ADP-ribosyl)ation (PARylation) executes a critical function in M. oryzae. M. oryzae Poly(ADP-ribose) polymerase 1 (PARP1) exhibits robust PARylation activity. Disruption of PARylation by PARP1 knock-out or chemical inhibition reveals its involvement in M. oryzae virulence, particularly in appressorium formation. Furthermore, we identified two M. oryzae 14-3-3 proteins, GRF1 and GRF2, as substrates of PARP1. Deletion of GRF1 or GRF2 results in delayed and dysfunctional appressorium, diminished plant penetration, and reduced virulence of the fungus. Biochemical and genetic evidence suggest that PARylation of 14-3-3s is essential for its function in M. oryzae virulence. Moreover, PARylation regulates 14-3-3 dimerization and is required for the activation of the mitogen-activated protein kinases (MAPKs), Pmk1 and Mps1. GRF1 interacts with both Mst7 and Pmk1, and bridges their interaction in a PARylation-dependent manner. This study unveils a distinctive mechanism that PARylation of 14-3-3 proteins controls appressorium formation through MAPK activation, and could facilitate the development of new strategies of rice blast disease control.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Predictive role of depressive symptoms on frailty and its components in Chinese middle-aged and older adults: a longitudinal analysis.

BACKGROUND: To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. METHOD: The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. RESULTS: At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665-7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324-3.631) and the long term (OR = 1.926, 95%CI 1.021-3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250-3.166), slowness (OR = 1.395, 95%CI 1.044-1.865), and exhaustion (OR = 2.827, 95%CI 2.150-3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004-4.109) onset during the long-term. CONCLUSION: Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.

Adipose-derived mesenchymal stem cells suppress fibroblast proliferation of hypertrophic scar through CCL5 and CXCL12.

BACKGROUND AND OBJECTIVE: Adipose-derived mesenchymal stem cells (ADSCs) can accelerate wound healing, reduce scar formation, and inhibit hypertrophic scar (HTS). ADSCs can secrete a large amount of CCL5, and CCL5 has been proved to be pro-inflammatory and pro-fibrotic. CXCL12 (SDF-1) is a key chemokine that promotes stem cell migration and survival. Therefore, this study selected normal skin and HTS conditioned medium to simulate different microenvironments, and analyzed the effects of different microenvironments on the expression of CCL5 and CXCL12 in human ADSCs (hADSCs). MATERIALS AND METHODS: hADSCs with silenced expression of CCL5 and CXCL12 were co-cultured with hypertrophic scar fibroblasts to verify the effects of CCL5 and CXCL12 in hADSCs on the proliferation ability of hypertrophic scar fibroblasts. A mouse model of hypertrophic scar was established to further confirm the effect of CCL5 and CXCL12 in hADSCs on hypertrophic scar formation. RESULTS: CCL5 level was found to be significantly high in hADSCs cultured in HTS conditioned medium. CXCL12 in HTS group was prominently lowly expressed compared with the normal group. Inhibition of CCL5 in hADSCs enhanced the effects of untreated hADSCs on proliferation of HTS fibroblasts while CXCL12 knockdown exerted the opposite function. Inhibition of CCL5 in hADSCs increased the percentage of HTS fibroblasts in the G0/G1 phase while down-regulation of CXCL12 decreased those. Meanwhile, the down-regulated levels of fibroblast markers including collagen I, collagen III, and α-SMA induced by CCL5 knockdown were significantly up-regulated by CXCL12 inhibition. hADSCs alleviate the HTS of mice through CCL5 and CXCL12. CONCLUSION: In summary, our results demonstrated that hADSCs efficiently cured HTS by suppressing proliferation of HTS fibroblasts, which may be related to the inhibition of CXCL12 and elevation of CCL5 in hADSCs, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of HTS.

The function and mechanism of LAPTM5 in diseases.

The Lysosomal Protein Transmembrane 5 (LAPTM5) is a lysosomal transmembrane protein preferentially expressed in hematopoietic cells. The human LAPTM5 gene is located at position 1p34 and extends approximately 25 kb. Its protein includes five transmembrane domains, three PY motifs, and one UIM. The PY and UIM motifs can interact with various substrates, mediating sorting of proteins from Golgi to lysosome and subsequently participating in intracellular substrate transport and lysosomal stability regulation. Overexpression of LAPTM5 can induce lysosomal cell death (LCD), although the integrity of LAPTM5 protein is necessary for maintaining lysosome stability. Furthermore, LAPTM5 plays a role in autophagy activation during disease processes and has been confirmed to be closely associated with the regulation of immunity and inflammation. Therefore, LAPTM5 regulates a wide range of physiological processes and is involved in various diseases. This article summarizes the characteristics of the LAPTM5 gene and protein structure and provides a comprehensive review of the mechanisms involved in cell death, autophagy, immunity, and inflammation regulation. It emphasizes the significance of LAPTM5 in the clinical prevention and treatment of cardiovascular diseases, immune system disorders, viral infections, cancer, and other diseases, which could provide new therapeutic ideas and targets for human diseases.

Clinical and genetic characteristics of a child with Sotos syndrome and attention-deficit/hyperactivity disorder: A case report.

BACKGROUND: Sotos syndrome is an autosomal dominant disorder, whereas attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition. This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty. CASE SUMMARY: The patient presented with accelerated growth and advanced skeletal maturation; however, she lacked any distinct facial characteristics related to specific genetic disorders. Genetic analyses revealed a paternally inherited heterozygous synonymous mutation [c.4605C>T (p.Arg1535Arg)]. Functional analyses suggested that this mutation may disrupt splicing, and bioinformatics analyses predicted that this mutation was likely pathogenic. After an initial diagnosis of Sotos syndrome, the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months. CONCLUSION: The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.