Identification of SGMS2 as a molecule involved in natural killer cell recruitment and its in-deep analysis in the liver cancer microenvironment: Evidence from large populations cohort.

BACKGROUND: Liver cancer, a common malignancy within the digestive system, presents with a particularly grim prognosis. Within the immune microenvironment, the role of natural killer (NK) cells in liver cancer remains unclear. METHODS: We sourced data on clinical parameters and gene expressions for liver cancer patients from The Cancer Genome Atlas Program database and carried out all analyses using R software and its relevant codes. RESULTS: In our research, we delved into the genes intertwined with NK cells in hepatocellular carcinoma (HCC). Leveraging the QUANTISEQ and MCPCOUNTER algorithms to quantify NK cells, we spotlighted genes vital to the recruitment of NK cells. Among these genes, GDE1, WDFY3, DNAJB14, PKD2, DGAT2, SGMS2 and MKNK2 showed a strong correlation with patient outcomes. We also mapped out the single-cell expression trajectories of these genes within the HCC milieu. From our findings, SGMS2 emerged as a key gene warranting further scrutiny. Our in-depth analysis of SGMS2 shed light on its influence over specific biological pathways, its contribution to the immune landscape and its role in genomic instability within HCC. Drawing from this, we formulated a predictive model rooted in SGMS2-associated genes. This model showcased remarkable precision across both training and validation cohorts. CONCLUSIONS: Overall, our investigation underscored the profound implications of SGMS2, a gene pivotal to NK cell infiltration, in the landscape of HCC, thereby positioning it as a potential linchpin in oncological strategies.

Clinical applications and perspectives of circulating tumor DNA in gastric cancer.

Gastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the blood. Numerous gastric cancer-specific ctDNA biomarkers have now been identified. CtDNA analysis provides insight into genetic and epigenetic alterations in tumors, holding promise for predicting treatment response and prognosis in gastric cancer patients. This review summarizes current research on ctDNA biology and detection technologies, while highlighting clinical applications of ctDNA for gastric cancer diagnosis, prognosis, and guiding treatment decisions. Current challenges and future perspectives for ctDNA analysis are also discussed.

Vinculin Identified as a Potential Biomarker in Hand-Arm Vibration Syndrome Based on iTRAQ and LC-MS/MS-Based Proteomic Analysis.

Local vibration can induce vascular injuries, one example is the hand-arm vibration syndrome (HAVS) caused by hand-transmitted vibration (HTV). Little is known about the molecular mechanism of HAVS-induced vascular injuries. Herein, the iTRAQ (isobaric tags for relative and absolute quantitation) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was applied to conduct the quantitative proteomic analysis of plasma from specimens with HTV exposure or HAVS diagnosis. Overall, 726 proteins were identified in iTRAQ. 37 proteins upregulated and 43 downregulated in HAVS. Moreover, 37 upregulated and 40 downregulated when comparing severe HAVS and mild HAVS. Among them, Vinculin (VCL) was found to be downregulated in the whole process of HAVS. The concentration of vinculin was further verified by ELISA, and the results suggested that the proteomics data was reliable. Bioinformative analyses were used, and those proteins mainly engaged in specific biological processes like binding, focal adhesion, and integrins. The potential of vinculin application in HAVS diagnosis was validated by the receiver operating characteristic curve.

Effect of Radial Artery Compression with a Novel Automatic Pressure-Controlled Radial Compression Device: A Short-Term Prospective Interventional Pilot Study.

This study was conducted to design a novel radial compression device with the function of automatic pressure control and evaluate the feasibility and safety of this new technique. Patients who underwent transradial access (TRA) coronary angiography and percutaneous coronary intervention (PCI) in the First Hospital of Jiaxing between August 2021and October 2021 were prospectively enrolled in this pilot interventional study. The patients were grouped in a 1 : 1 ratio to receive compression with a novel device (the experimental group) or a conventional device without pressure control (the control group). The primary endpoint was the compression time, and the main secondary endpoints were rebleeding, upper-limb swelling, radial artery occlusion (RAO), and device-related pressure injury (DPI). Eighty-four patients were enrolled in this study. No significant differences were found in the baseline clinical characteristics between the two groups. Compared with the control group, the compression time in the experimental group was significantly reduced (207.4 ± 15.5 vs. 378.1 ± 19 min, p < 0.001). Besides, the rate of upper-limb swelling was also significantly lower in the novel device group (2.4% vs. 85.7%, p < 0.001), as well as the rate of DPI (19.05% vs. 100%, p = 0.005). Furthermore, the pain score in the experimental group was significantly lower than in the control group (0.79 ± 0.42 vs. 1.83 ± 0.58, p < 0.001). There were no significant differences in the rate of rebleeding (7.1% vs. 14.3, p = 0.48) between the two groups. In addition, no RAO occurred in any of the groups. The novel automatic pressure-controlled radial compression device could reduce the hemostasis time and decrease the rate of adverse complications. It might be a promising and effective compression device in TRA coronary invasive procedures.

The prevalence and risk factors of work related musculoskeletal disorders among electronics manufacturing workers: a cross-sectional analytical study in China.

OBJECTIVES: To describe the prevalence of self-reported musculoskeletal disorders among workers in the electronics manufacturing industry and to investigate the relations between work-related musculoskeletal disorders (WMSDs) and work-related variables. METHODS: An interview-based questionnaire survey was carried out in thirty electronics manufacturing factories in China in 2018. The prevalence of WMSDs was estimated using the modified Nordic Musculoskeletal Questionnaire (NMQ). A multivariate logistic regression model was applied to evaluate the effects of risk factors on WMSDs on multiple body parts. RESULTS: The 12-month prevalence of WMSDs among participants was 40.6%, and the common body sites affected were the neck (26.8%), shoulder (22.8%), upper back (14.9%), and lower back (14.8%). The results of logistic regression showed that female adults, > 5 job tenure and work-related factors (including awkward posture, lifting or carrying weights, excessive repetition, prolonged sitting, monotonous work and working under conditions of cold or temperature variations) led to a higher risk of WMSDs on most body parts. Upper back, wrist/hand and elbow pain levels were significantly higher for workers with vibration. However, more frequently, physical exercise was a protective factor against WMSDs on most body parts except the upper back, leg and knee. CONCLUSIONS: The study indicates a high prevalence of musculoskeletal pain among the electronics manufacturing industry in China. Different personal and work factors are related to the occurrence of WMSD on different body parts. Preventive measures should be implemented based on the characteristics of WMSD in the electronic manufacturing industry. Furthermore, the training and intervention guidance of ergonomic hazards in the workplace need to be strengthened by understanding the impact of bad posture, avoiding long-term sitting posture and increasing physical activities.

Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway.

OBJECTIVES: To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI. MATERIALS AND METHODS: C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine. RESULTS: Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naïve CD4+ T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells. CONCLUSIONS: DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naïve CD4+ T cells via activating the AMPK/SIRT1 pathway.

Comprehensive Investigation Illustrates the Role of M2 Macrophages and Its Related Genes in Pancreatic Cancer.

Background and Objectives: M2 macrophages play an important role in cancers. Our study aimed to illustrate the effect of M2 macrophages in pancreatic cancer (PC). Materials and Methods: The open-access data used for analysis were downloaded from The Cancer Genome Atlas Program database, as well as some online databases. R software was mainly used for data analysis based on the specific packages. Results: Here, we comprehensively investigated the role of M2 macrophages and their related genes in PC. We performed the biological enrichment of M2 macrophages in PC. Meanwhile, we identified adenosine A3 receptor (TMIGD3) as the interest gene for further analysis. The single-cell analysis showed that was mainly expressed in the Mono/Macro cells based on the data from multiple data cohorts. Biological investigation showed that TMIGD3 was primarily enriched in angiogenesis, pancreas-beta cells and TGF-beta signaling. Tumor microenvironment analysis indicated that TMIGD3 was positively correlated with monocyte_MCPCOUNTER, NK cell_MCPCOUNTER, macrophages M2_CIBERSORT, macrophage_EPIC, neutrophil_TIMER and endothelial cell_MCPCOUNTER. Interestingly, we determined that all the immune functions quantified by single sample gene set enrichment analysis algorithms were activated in the patients with high TMIGD3 expression. Conclusions: Our results provide a novel direction for the research focused on the M2 macrophages in PC. Meanwhile, TMIGD3 was identified as an M2 macrophage-related biomarker for PC.

lncRNA-AC079061.1/VIPR1 axis may suppress the development of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. METHODS: Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. RESULTS: lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. CONCLUSION: The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.

Prevalence and risk factors analysis for low back pain among occupational groups in key industries of China.

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.

Shoulder work-related musculoskeletal disorders and related factors of workers in 15 industries of China: a cross-sectional study.

BACKGROUND: Changes in modern industrial production practices can easily lead to shoulder work-related musculoskeletal disorders (WMSD). The current reports on shoulder WMSD are limited to some industries are less well studied, and the sample size is usually small. This study aimed to describe the prevalence and severity of shoulder WMSD in a large sample of Chinese workers from 15 industries, analyze the possible correlations with sociodemographic and work-related variables, and compare the differences between industries. METHODS: A cross-sectional study was conducted among a sample of 55,749 participants from 252 enterprises in 15 industries throughout China. A Chinese version of the musculoskeletal disease questionnaire was used to collect the demographic factors, shoulder symptoms in past 12 months, and work-related factors including posture-related factors, repetition, vibration, work organization, job control, and environmental factors as independent variables. Descriptive statistics were used, and the binary logistic regression analysis was performed to explore the association between shoulder WMSD and potential demographic and work-related factors. RESULTS: Nearly 35.5% of participants reported shoulder pain and discomfort in the previous 12 months. Biopharmaceutical manufacturing (56.2%), medical services (54.4%), and aviation services (50.1%) were the three industries with the highest prevalence of shoulder WMSD. The pain score of aviation services workers was the highest. The related factors for shoulder WMSD varied among the different industries. CONCLUSION: Our study found a relatively high prevalence of shoulder WMSD in China. There were large differences in the prevalence of shoulder WMSD among industries, and the related factors were particular to each industry. Such information is useful to help occupational health practitioners and policymakers conduct preventive programs to reduce shoulder disorders in these working populations.

Association between paternal age and singleton birthweight in frozen embryo transfer cycles.

BACKGROUND: Many studies have considered maternal age as a determinant factor for success in assisted reproductive technologies (ART), but the potential role of paternal age on neonatal outcomes has been overlooked. This study aimed to explore the association between paternal age and birthweight in frozen embryo transfer (FET) cycles. METHODS: This retrospective study involved singleton live births born to women undergoing frozen embryo transfer from January 2013 to December 2017 at a tertiary care center in Shanghai, China. The paternal age was classified into four categories: ≤ 30, 31-35, 36-40, and ≥ 41 years. The group consisting of respondents with paternal age of 31-35 was set as the reference group. Singleton birthweight was the primary outcome measure. Z-scores were calculated according to gestational age and newborn gender on birthweight based on the national birthweight reference. Multivariable linear regression analysis was performed to reveal the relationship between paternal age and newborns' birthweight after considering several potential confounders. RESULTS: Exactly 9765 women who fulfilled the inclusion criteria were enrolled. No significant difference was found on mean birthweight (P = 0.082) and gestation-adjusted Z-scores (P = 0.569) among paternal age categories. The reference group and the group with aged 36-40 years had the highest mean birthweight and Z-scores, respectively (3350.2 ± 467.8 g, 0.36 ± 1.00). A decline in mean birthweight with paternal age was observed, and the group over 40 years had the lowest value of 3309.4 ± 474.3 g, but the difference was not statistically significant. In multivariate analyses, the adjusted odds of very low birthweight (LBW), LBW, and high birthweight in the reference group did not significantly differ with the three other groups. After correcting several potential confounders, no significant correlation was observed between paternal age and neonatal birthweight (P = 0.289). CONCLUSION: Paternal age was not associated with mean birthweight and gestational age- and gender-adjusted birthweight (Z-scores) of singletons among women who became pregnant in FET cycles.

Cold water immersion test (10 °C, 10 min) for diagnosing vibration-induced white finger among a group of polishers in a subtropical environment.

OBJECTIVE: This study aimed to investigate whether the finger skin temperature (FST) after cold provocation (10 °C, 10 min) is as a useful indicator for assisting in the diagnosis of vibration-induced white finger (VWF) in a group of polishers in a subtropical environment. METHOD: Ninety male vibration-exposed metal polishers (30 patients and 60 controls) from the Guangdong Province in Southern China were recruited. The FSTs at 30, 20, 10, and 0 min before cold water immersion (FSTpre-30, FSTpre-20, FSTpre-10, and FSTbaseline) and 0, 5, 10, 15, 20, 25, and 30 min after immersion (FST0, FST5, FST10, FST15, FST20, FST25, and FST30) were measured on the index, middle, and ring fingers of both hands. RESULTS: During the first 20-min adaptation period, there was a significant increase in FST in three fingers on both hands in the two groups. In contrast, there were no significant differences between FSTpre-10 and FSTbaseline. Furthermore, FSTpre-30, FSTpre-20, FSTpre-10, and FSTbaseline of the three fingers in both hands did not differ significantly. During recovery, the indicators FST5-0, FST10-0, R5, and R10 for the index finger of the left hand in patients were lower than for the controls. Among the various indicators, the absolute recovery rate, FST5-0, at 5 min after immersion was identified as the best diagnosis indicator with a sensitivity of 76.7% and specificity of 70.0% when applied to the index finger of the left hand. CONCLUSION: The cold water immersion test as applied in a subtropical environment can have a fair discriminating ability for diagnosing VWF.

Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer.

BACKGROUND: Many novel diagnostic biomarkers have been developed for gastric cancer (GC) recently. We chose two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models. METHODS: We reviewed the diagnostic accuracies of all microRNAs identified by previous diagnostic tests. Then appropriate microRNAs and their combinations were validated the diagnostic value. We included 80 patients with GC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was conducted, and we used three multivariate statistical analyses to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models. RESULTS: Sixty-seven published studies and 70 microRNAs were finally included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a and miR-421 were chosen to further validate their diagnostic efficiencies. Five of those microRNAs in GC patients had significantly different expression. The combination of miR-19a and miR-92a had the highest area under the curve (AUC) at 0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis performed an excellent diagnostic value and the AUC reached 1.0. CONCLUSION: There is a good potential for microRNAs and GC/MS analysis as new diagnostic methods in view of their high diagnostic value compared with traditional biomarkers.

Vibration characteristics of golf club heads in their handheld grinding process and potential approaches for reducing the vibration exposure.

To control vibration-induced white finger among workers performing the fine grinding of golf club heads, the aims of this study are to clarify the major vibration sources in the grinding process, to identify and understand the basic characteristics of the club head vibration, and to propose potential approaches for reducing the vibration exposure. The vibrations on two typical club heads and two belt grinding machines were measured at a workplace. A simulated test station was also constructed and used to help examine some influencing factors of the club head vibration. This study found that the club head vibration was the combination of the vibration transmitted from the grinding machines and that generated in the grinding process. As a result, any factor that affects the machine vibration, the grinding vibration, and/or the dynamic response of the club head can influence the vibration exposure of the fingers or hands holding the club head in the grinding process. The significant influencing factors identified in the study include testing subject, grinding machine, machine operation speed, drive wheel condition, club head model, mechanical constraints imposed on the club head during the grinding, and machine foot pad. These findings suggest that the vibration exposure can be controlled by reducing the grinding machine vibration, changing the workpiece dynamic properties, and mitigating the vibration transmission in its pathway. Many potential methods for the control are proposed and discussed. RELEVANCE TO INDUSTRY: Vibrations on handheld workpieces can be effectively transmitted to the hands, especially the fingers. As a result, a major component of the hand-arm vibration syndrome - vibration-induced white finger - has been observed among some workers performing the grinding and/or polishing tasks of the handheld workpieces such as golf club heads. The results of this study can be used to develop more effective methods and technologies to control the vibration exposure of these workers. This may help effectively control this occupational disease.

RNA binding protein Nova1 promotes tumor growth in vivo and its potential mechanism as an oncogene may due to its interaction with GABAA Receptor-γ2.

BACKGROUND: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAA receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1. METHODS: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma. In vivo tumorigenticity test was conducted in nude mice by regulation the expression of Nova1. Later, western blot and co-immunoprecipitation were carried out to verify the interaction between Nova1 and GABAARγ2 in HCC tissue. RESULTS: Immunohistochemical staining showed GABAARγ2 expression in HCC. Survival analysis showed intratumoral GABAARγ2 was an independent prognostic factor for overall survival (OS) and disease free survival (DFS). Up-regulation of Nova1 expression promotes subcutaneous HCC growth in nude mice and western blot showed the ectopic expression of Nova-1 restro-regulates the expression of GABAARγ2 and GABA. Protein level interaction of GABAARγ2 and Nova-1 was evidenced by co-immunoprecipitation. CONCLUSIONS: Nova1 interacts with GABAARγ2 not only in CNS but also in HCC. Nova1's potential mechanism as an oncogene may due to its interaction with GABAA Rγ2. A better understanding of the mechanism of Nova1 for HCC progression provides a novel target for an optimal immunotherapy against this fatal malignancy.

Development of an efficient liposomal DOX delivery formulation for HCC therapy by targeting CK2α.

Hepatocellular carcinoma (HCC) is a digestive tract cancer with high mortality and poor prognosis, especially in China. Current chemotherapeutic drugs lead to poor prognosis, low efficacy, and high side effects due to weak targeting specificity and rapidly formed multidrug resistance (MDR). Based on the previous studies on the doxorubicin (DOX) formulation for cancer targeting therapy, we developed a novel DOX delivery formulation for the targeting chemotherapy of HCC and DOX resistant HCC. HCSP4 was previously screened and casein kinase 2α (CK2α) was predicted as its specific target on HCC cells in our lab. In the study, miR125a-5p was firstly predicted as an MDR inhibiting miRNA, and then CK2α was validated as the target of HCSP4 and miR125a-5p using CK2α-/-HepG2 cells. Based on the above, an HCC targeting and MDR inhibiting DOX delivery liposomal formulation, HCSP4/Lipo-DOX/miR125a-5p was synthesized and tested for its HCC therapeutic efficacy in vitro. The results showed that the liposomal DOX delivery formulation targeted to HCC cells specifically and sensitively, and presented the satisfied therapeutic efficacy for HCC, particularly for DOX resistant HCC. The potential therapeutic mechanism of the DOX delivery formulation was explored, and the formulation inhibited the expression of MDR-relevant genes including ATP-binding cassette subfamily B member 1 (ABCB1, also known as P-glycoprotein), ATP-binding cassette subfamily C member 5 (ABCC5), enhancer of zeste homolog 2 (EZH2), and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). Our study presents a novel targeting chemotherapeutic drug formulation for the therapy of HCC, especially for drug resistant HCC, although it is primarily and needs further study in vivo, but provided a new strategy for the development of novel anticancer drugs.

Differences in nature killer cell response and interference with mitochondrial DNA induced apoptosis in moxifloxacin environment.

OBJECTIVES: As antibiotics become more prevalent, accuracy and safety are critical. Moxifloxacin (MXF) have been reported to have immunomodulatory effects on a variety of immune cells and even anti-proliferative and pro-apoptotic effects, but the mechanism of action is not fully clear. METHODS: Peripheral blood mononuclear cells (PBMC) from experimental groups of healthy adults (n = 3) were treated with MXF (10ug/ml) in vitro for 24 h. Single-cell sequencing was performed to investigate differences in the response of each immune cell to MXF. Flow cytometry determined differential gene expression in subsets of most damaged NK cells. Pseudo-time analysis identified drivers that influence MXF-stimulated cell differentiation. Detection of mitochondrial DNA and its involvement in the mitochondrial respiratory chain pathway clarifies the origin of MXF-induced stress injury. RESULTS: Moxifloxacin-environmental NK cells are markedly reduced: a new subset of NK cells emerges, and immediate-early-response genes in this subset indicate the presence of an early activation response. The inhibitory receptor-dominant subset shows enhanced activation, leading to increased expression of cytokines and chemokines. The near-mature subset showed greater cytotoxicity and the most pronounced cellular damage. CD56bright cells responded by antagonizing the regulation of activation and inhibitory signals, demonstrating a strong cleavage capacity. The severe depletion of mitochondrial genes was focused on apoptosis induced by the mitochondrial respiratory chain complex. CONCLUSION: NK cells exhibit heightened sensitivity to the MXF environment. Different NK subsets upregulate the expression of cytokines and chemokines through different activation pathways. Concurrently, MXF induces impairment of the mitochondrial oxidative phosphorylation system, culminating in apoptosis.

Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting ß-catenin/TGF-ß1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.

Risk and related factors of elbow musculoskeletal diseases: A nationwide cross-sectional survey in China.

OBJECTIVE: Although studies have shown that Work-related Musculoskeletal Disorders (WMSDs) are common and continue to be a main source of disability and work time loss, there are few reports on elbow WMSDs. The aim of this study was to explore the prevalence and associated factors of elbow WMSDs. METHODS: The valid questionnaires of 57501 workers from 15 different industries nationwide were collected and the Chi-square test and logistic-regression-analysis were applied to reveal the prevalence and risk factors of elbow. RESULTS: The findings indicated that prevalence of elbow WMSDs among workers was 7.3%. The prevalence of elbow WMSDs in toy manufacturing was 21.3%, which significantly higher than that in other industries (P<0.05). Logistic regression analysis showed that aged 40 and above, married, very poor health, left-handed, lifting weights (more than 20 kg each time) , work requiring upper limb or hand force, work in an uncomfortable position, repetitive operations within one minute, using vibrating tools, work involves cold, cool winds or temperature changes, work being completed in the same workshop, work being done outdoors, frequent deal with customers , two shifts, often work overtime, staff shortage, often work for colleagues were the risk factors of elbow WMSDs.The higer education level and monthly income, and enough rest time were the protective factors of elbow WMSDs. CONCLUSION: The toy manufacturing is a high-risk industry for elbow WMSDs. The publicity and education of ergonomics knowledge should be strengthened, and the workers' ergonomics awareness should be improved to reduce the impact of WMSDs.

A NETWORK PHARMACOLOGY-BASED TREATMENT ANALYSIS OF LUTEOLIN FOR REGULATING PYROPTOSIS IN ACUTE LUNG INJURY.

ABSTRACT: Background: Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome, are complicated pulmonary inflammatory conditions for which standard therapeutics are still not well established. Although increasing research has indicated the anti-inflammatory, anticancer, and antioxidant effects of luteolin, especially in lung diseases, the molecular mechanisms underlying luteolin treatment remain largely unclear. Methods: The potential targets of luteolin in ALI were explored using a network pharmacology-based strategy and further validated in a clinical database. The relevant targets of luteolin and ALI were first obtained, and the key target genes were analyzed using a protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The targets of luteolin and ALI were then combined to ascertain the relevant pyroptosis targets, followed by Gene Ontology analysis of core genes and molecular docking of key active compounds to the antipyroptosis targets of luteolin in resolving ALI. The expression of the obtained genes was verified using the Gene Expression Omnibus database. In vivo and in vitro experiments were performed to explore the potential therapeutic effects and mechanisms of action of luteolin against ALI. Results: Fifty key genes and 109 luteolin pathways for ALI treatment were identified through network pharmacology. Key target genes of luteolin for treating ALI via pyroptosis were identified. The most significant target genes of luteolin in ALI resolution included AKT1, NOS2, and CTSG. Compared with controls, patients with ALI had lower AKT1 expression and higher CTSG expression. Luteolin simply reduced systemic inflammation and lung tissue damage in septic mice. Furthermore, we blocked AKT1 expression and found luteolin reduced the degree of lung injury and affected NOS2 levels. Conclusions: As demonstrated by a network pharmacology approach, luteolin may exert an antipyroptosis effect on ALI via AKT1, NOS2, and CTSG.