Sensory neuronal control of skin barrier immunity.

Peripheral sensory neurons recognize diverse noxious stimuli, including microbial products and allergens traditionally thought to be targets of the mammalian immune system. Activation of sensory neurons by these stimuli leads to pain and itch responses as well as the release of neuropeptides that interact with their cognate receptors expressed on immune cells, such as dendritic cells (DCs). Neuronal control of immune cell function through neuropeptide release not only affects local inflammatory responses but can impact adaptive immune responses through downstream effects on T cell priming. Numerous neuropeptide receptors are expressed by DCs but only a few have been characterized, presenting opportunities for further investigation of the pathways by which cutaneous neuroimmune interactions modulate host immunity.

Association of Oral Microbiome With Oral Human Papillomavirus Infection: A Population Study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: A cross-sectional analysis of 5496 20-59-year-old participants in the 2009-2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for ß-diversity (between-sample heterogeneity). RESULTS: Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = .992-.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI = .90-.99) were associated with high-risk oral HPV infection. ß-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045). There were differential associations when stratified by sex. CONCLUSIONS: Both oral microbiome α-diversity and ß-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Validation of self-reported male circumcision status and genital ulcer disease among Ugandan men.

OBJECTIVE: Voluntary medical male circumcision (MC) is a critical tool in combination HIV prevention programmes in Africa. Self-reported MC (SrMC) status is used in HIV epidemiological surveys to assess MC coverage but is subject to response bias with limited validation. This study evaluated the utility of SrMC status as a marker of MC as well as self-reported genital lesions for genital ulcer disease (GUD) among Ugandan men. METHODS: Male participants aged 18-49 years in the cross-sectional Sexually Transmitted Infection Prevalence study, conducted between May and October 2019, responded to a questionnaire capturing SrMC status and current genital ulcer symptoms followed by clinical assessment to verify MC and presence of GUD.Sensitivity, specificity, positive predictive value, negative predictive value and corresponding CIs (95% CI) for SrMC status and GUD were estimated. RESULTS: There were 853 male participants, of whom 470 (55.1%) self-reported being circumcised and 23 (2.7%) self-reported GUD (SrGUD). MC was clinically confirmed in 50.2% (n=428) of participants with sensitivity of SrMC status at 99% (95% CI: 98% to 100%) and specificity 89% (95% CI: 86% to 92%). Specificity of SrMC was lowest among persons living with HIV and viremic (>1000 copies/mL) at 72% (95% CI: 46% to 90%). 18 participants had clinically confirmed GUD, but only 12 SrGUD symptoms, corresponding to a sensitivity and specificity of 67% (95% CI: 41% to 87%) and 99% (95% CI: 98% to 99%), respectively. CONCLUSIONS: SrMC status is a robust proxy for clinically confirmed MC status and may reliably be used to assess MC coverage in this setting. Conversely, GUD symptoms were under-reported, which may impact effective syndromic management of sexually transmitted infections and warrants further examination.

Sexually transmitted infections and migration in Uganda: a population-based study.

OBJECTIVES: Migration is associated with increased risk of HIV infection in Africa, but evidence about non-HIV sexually transmitted infection (STI) burden among African migrants is limited. METHODS: We used data from the Sexually Transmitted Infection Prevalence Study, a cross-sectional population-based study of chlamydia, gonorrhoea, trichomoniasis, syphilis and herpes simplex virus type 2 prevalence in southern Uganda, to compare STI prevalence between adults aged 18 and 49 years with and without a recent history of migration. Migration status was determined using household census data, with a recent migration history defined as having moved into one's community of current residence within the last ~18 months. Unadjusted and adjusted modified Poisson regression models were used to compare individual STI prevalence risk by recent migration status with associations reported as adjusted prevalence risk ratios (adjPRRs) with 95% CIs. Adjusted models included participants' sex, age, community type, education, occupation and marital status. RESULTS: Among 1825 participants, 358 (19.6%) had a recent migration history. Overall, migrants exhibited a significantly higher combined prevalence of curable STIs (gonorrhoea, chlamydia, high-titre syphilis (rapid plasma regain ≥1:8) and trichomoniasis) as compared with long-term residents (34.4% vs 24.2%; adjPRR=1.23; 95% CI 1.03 to 1.47). Significant differences in curable STI prevalence by migration status were concentrated among persons living with HIV (49.4% prevalence in migrants vs 32.6% in long-term residents; adjPRR=1.42; 95% CI 1.10 to 1.85) and among women (38.8% in migrants vs 27.8% in long-term residents; adjPRR=1.26; 95% CI 1.01 to 1.58). High-titre syphilis prevalence was especially elevated among male migrants (11.2% in migrants vs 4.9% in long-term residents; adjPRR=1.82; 95% CI 1.06 to 3.13). CONCLUSIONS: The prevalence of non-HIV STIs is higher among migrants. Tailored outreach and service delivery approaches that address the needs of mobile populations are crucial for integrated HIV and STI epidemic control in Uganda to optimise resources and reduce transmission risks.

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

BACKGROUND: Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). STUDY DESIGN AND METHODS: We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. RESULTS: Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. CONCLUSION: Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

Chronic automated red cell exchange therapy for sickle cell disease.

BACKGROUND: The data to support chronic automated red cell exchange (RCE) in sickle cell disease (SCD) outside of stroke prevention, is limited, especially in adults. STUDY DESIGN AND METHODS: A retrospective analysis was conducted of patients with SCD who were referred for chronic RCE at our institution over a 10-year period. Data that were evaluated included patient demographics, referral indications, and procedural details (e.g., vascular access, adverse events, etc.). In a subanalysis, the number of annual acute care encounters during 3 years of chronic RCE was compared with that in the year preceding the first RCE. RESULTS: A total of 164 patients were referred for chronic RCE: median age was 28 years (interquartile range [IQR] = 22-36) at referral and 60% were female. Seventy (42.6%) were naïve to chronic transfusion (simple or RCE) prior to referral. The leading indications for referral were refractory pain (73/164, 44.5%) and iron overload (57/164, 34.7%). A total of 5090 procedures occurred during the study period (median = 19, IQR = 5-45). Of the 138 patients who had central vascular access, 8 (6%) and 16 (12%) had ≥1 central-line-related thrombosis and/or infection, respectively. Of those who were not RBC alloimmunized at initiation of RCE, 12/105 (11.4%) developed new antibodies during chronic RCE. In those 30 patients who were adherent to therapy for 3 years, there was no significant difference in acute care encounters following initiation of RCE. CONCLUSION: Prospective clinical trials are needed to determine which patients are most likely to benefit from chronic RCE and refine selection accordingly.

The efficacy of 1-allyloxy-4-propoxybenzene (3c{3,6}) against Varroa destructor mites in honey bee colonies from Maryland, USA.

Varroa destructor Oud (Acari: Varroidae) is a harmful ectoparasite of Apis mellifera L. honey bees causing widespread colony losses in Europe and North America. To control populations of these mites, beekeepers have an arsenal of different treatments, including both chemical and nonchemical options. However, nonchemical treatments can be labor intensive, and Varroa has gained resistance to some conventional pesticides, and the use of other chemical treatments is restricted temporally (e.g., cannot be applied during periods of honey production). Thus, beekeepers require additional treatment options for controlling mite populations. The compound 1-allyloxy-4-propoxybenzene (3c{3,6}) is a diether previously shown to be a strong feeding deterrent against Lepidopteran larvae and a repellent against mosquitoes and showed promise as a novel acaricide from laboratory and early field trials. Here we test the effect of the compound, applied at 8 g/brood box on wooden release devices, on honey bees and Varroa in field honey bee colonies located in Maryland, USA, and using a thymol-based commercial product as a positive control. 3c{3,6} had minimal effect on honey bee colonies, but more tests are needed to determine whether it affected egg production by queens. Against Varroa3c{3,6} had an estimated efficacy of 78.5%, while the positive control thymol product showed an efficacy of 91.3%. 3c{3,6} is still in the development stage, and the dose or application method needs to be revisited.

PTBP1 plays an important role in the development of gastric cancer.

BACKGROUND: Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. METHODS: We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. RESULTS: Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. CONCLUSIONS: Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.

Customizable Machine-Learning Models for Rapid Microplastic Identification Using Raman Microscopy.

Raman spectroscopy is commonly used in microplastics identification, but equipment variations yield inconsistent data structures that disrupt the development of communal analytical tools. We report a strategy to overcome the issue using a database of high-resolution, full-window Raman spectra. This approach enables customizable analytical tools to be easily created─a feature we demonstrate by creating machine-learning classification models using open-source random-forest, K-nearest neighbors, and multi-layer perceptron algorithms. These models yield >95% classification accuracy when trained on spectroscopic data with spectroscopic data downgraded to 1, 2, 4, or 8 cm-1 spacings in Raman shift. The accuracy can be maintained even in non-ideal conditions, such as with spectroscopic sampling rates of 1 kHz and when microplastic particles are outside the focal plane of the laser. This approach enables the creation of classification models that are robust and adaptable to varied spectrometer setups and experimental needs.

Betulonic Acid, as One of the Active Components of the Celastrus orbiculatus Extract, Inhibits the Invasion and Metastasis of Gastric Cancer Cells by Mediating Cytoskeleton Rearrangement In Vitro.

Gastric cancer is a type of malignant tumor that seriously threatens human life and health. Invasion and metastasis present difficulties in the treatment of gastric cancer, and the remodeling of the tumor cytoskeleton plays an important role in mediating the ability of tumor cells to achieve invasion and metastasis. Previous experimental results suggest that Celastrus orbiculatus extract can regulate cytoskeletal remodeling in gastric cancer, but the active component has not been determined. Betulonic acid, as an effective component of COE, inhibits the invasion and metastasis of gastric cancer cells by regulating cytoskeletal remodeling in vitro; its specific mechanisms have been studied here. After betulonic acid was dissolved, it was diluted to various working concentrations in RPMI-1640 medium and added to AGS, HGC-27 and GES-1 cell lines. Cell viability was assessed by CCK-8 and colony formation assays. Cytoskeleton staining was used to detect changes in cytoskeleton morphology. Functional assays including wound healing assays and transwell assays were used to detect the invasion and migration of cells. The effect of betulonic acid on cell invasion and migration was clearly and precisely observed by high-content imaging technology. Western blotting was used to detect the regulation of matrix metalloproteinase-related proteins and epithelial-mesenchymal transformation-related proteins. We found that betulonic acid inhibited the migration and invasion of gastric cancer cells. Therefore, betulonic acid inhibits the invasion and metastasis of gastric cancer cells by mediating cytoskeletal remodeling and regulating epithelial mesenchymal transformation.

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells.

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.

Integration of glutathione disulfide-mediated extraction and capillary electrophoresis for determination of Cd(II) and Pb(II) in edible oils.

A novel method is introduced for extracting and enriching Cd(II) and Pb(II) from edible oils using glutathione disulfide (GSSG) as both an extractant and a phase-separation agent. The ions in the oils were initially extracted into an aqueous solution containing GSSG. After mixing the solution with acetonitrile at the appropriate volume ratio, a new phase formed, resulting in enrichment of the analytes. The experimental conditions were optimized using response surface methodology with a central composite design. Under optimal conditions, the method offered a combined enrichment factor of >660, with combined extraction efficiencies of 84.31% and 83.35% for Cd(II) and Pb(II), respectively. Finally, the method was conjugated to capillary electrophoresis to determine Cd(II) and Pb(II) in edible oil samples, with detection limits of 0.45 and 1.24 ppb, respectively. In comparison to traditional approaches, the GSSG-based method demonstrates rapidity, efficiency, and recyclability in extracting heavy metal ions from complex matrices.

Efficient removal of phosphorus and nitrogen from aquatic environment using sepiolite-MgO nanocomposites: preparation, characterization, removal performance, and mechanism.

Excessive phosphorus will lead to eutrophication in aquatic environment; the efficient removal of phosphorus is crucial for wastewater engineering and surface water management. This study aimed to fabricate a nanorod-like sepiolite-supported MgO (S-MgO) nanocomposite with high specific surface area for efficient phosphate removal using a facile microwave-assisted method and calcining processes. The impact of solution pH, adsorbent dosage, contact time, initial phosphate concentrations, Ca2+ addition, and N/P ratio on the phosphate removal was extensively examined by the batch experiments. The findings demonstrated that the S-MgO nanocomposite exhibited effective removal performance for low-level phosphate (0 ~ 2.0 mM) within the pH range of 3.0 ~ 10.0. Additionally, the nanocomposite can synchronously remove phosphate and ammonium in high-level nutrient conditions (> 2.0 mM), with the maximum removal capacities of 188.49 mg P/g and 89.78 mg N/g. Quantitative and qualitative analyses confirmed the successful harvesting of struvite in effluent with high-phosphate concentrations, with the mechanisms involved attributed to a synergistic combination of sorption and struvite crystallization. Due to its proficient phosphate removal efficiency, cost-effectiveness, and substantial removal capacity, the developed S-MgO nanocomposite exhibits promising potential for application in phosphorus removal from aquatic environments.

Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

Predicting the Risk of Loneliness in Children and Adolescents: A Machine Learning Study.

BACKGROUND: Loneliness is increasingly emerging as a significant public health problem in children and adolescents. Predicting loneliness and finding its risk factors in children and adolescents is lacking and necessary, and would greatly help determine intervention actions. OBJECTIVE: This study aimed to find appropriate machine learning techniques to predict loneliness and its associated risk factors among schoolchildren. METHODS: The data were collected from an ongoing prospective puberty cohort that was established in Chongqing, Southwest China. This study used 822 subjects (46.84% boys, age range: 11-16) followed in 2019. Five models, (a) random forest, (b) extreme gradient boosting (XGBoost), (c) logistic regression, (d) neural network, and (e) support vector machine were applied to predict loneliness. A total of 39 indicators were collected and 28 predictors were finally included for prediction after data pre-processing, including demographic, parental relationship, mental health, pubertal development, behaviors, and environmental factors. Model performance was determined by accuracy and AUC. Additionally, random forest and XGBoost were applied to identify the important factors. The XGBoost algorithm with SHAP was also used to interpret the results of our ML model. RESULTS: All machine learning performed with favorable accuracy. Compared to random forest (AUC: 0.87 (95%CI: 0.80, 0.93)), logistic regression (AUC: 0.80 (95%CI: 0.70, 0.89)), neural network (AUC: 0.80 (95%CI: 0.71, 0.89)), and support vector machine (AUC: 0.79 (95%CI: 0.79, 0.89)), XGBoost algorithm had the highest AUC values 0.87 (95%CI: 0.80, 0.93) in the test set, although the difference was not significant between models. Peer communication, index of general affect, peer alienation, and internet addiction were the top four significant factors of loneliness in children and adolescents. CONCLUSIONS: The results of this study suggest that machine learning has considerable potential to predict loneliness in children. This may be valuable for the early identification and intervention of loneliness.

Neuronal ferroptosis and ferroptosis-mediated endoplasmic reticulum stress: Implications in cognitive dysfunction induced by chronic intermittent hypoxia in mice.

Obstructive sleep apnea, typically characterized by chronic intermittent hypoxia (CIH), is linked to cognitive dysfunction in children. Ferroptosis, a novel form of cell death characterized by lethal iron accumulation and lipid peroxidation, is implicated in neurodegenerative diseases and ischemia-reperfusion injuries. Nevertheless, its contribution to CIH-induced cognitive dysfunction and its interaction with endoplasmic reticulum stress (ERS) remain uncertain. In this study, utilizing a CIH model in 4-week-old male mice, we investigated ferroptosis and its potential involvement in ERS regulation during cognitive dysfunction. Our findings indicate ferroptosis activation in prefrontal cortex neurons, leading to neuron loss, mitochondrial damage, decreased levels of GPX4, SLC7A11, FTL, and FTH, increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), Fe2+, ACSL4, TFRC, along with the activation of ERS-related PERK-ATF4-CHOP pathway. Treatment with the ferroptosis inhibitor liproxstatin-1 (Lip-1) and the iron chelator deferoxamine (DFO) effectively mitigated the neuron injury and cognitive dysfunction induced by CIH, significantly reducing Fe2+ and partly restoring expression levels of ferroptosis-related proteins. Furhermore, the use of Lip-1 and DFO downregulated p-PERK, ATF4 and CHOP, and upregulated Nrf2 expression, suggesting that inhibiting ferroptosis reduce ERS and that the transcription factor Nrf2 is involved in the process. In summary, our findings indicate that cognitive impairment in CIH mice correlates with the induction of neuronal ferroptosis, facilitated by the System xc - GPX4 functional axis, lipid peroxidation, and the iron metabolism pathway, along with ferroptosis-mediated ERS in the prefrontal cortex. Nrf2 has been identified as a potential regulator of ferroptosis and ERS involved in the context of CIH.

Identification of S100A8/A9 involved in thromboangiitis obliterans development using tandem mass tags-labeled quantitative proteomics analysis.

Thromboangiitis obliterans (TAO) is characterized by inflammation and obstruction of small-and medium-sized distal arteries, with limited pharmacotherapies and surgical interventions. The precise pathogenesis of TAO remains elusive. By utilizing the technology of tandem mass tags (TMT) for quantitative proteomics and leveraging bioinformatics tools, a comparative analysis of protein profiles was conducted between normal and TAO rats to identify key proteins driving TAO development. The results unveiled 1385 differentially expressed proteins (DEPs) in the TAO compared with the normal group-comprising 365 proteins with upregulated expression and 1020 proteins with downregulated expression. Function annotation through gene ontology indicated these DEPs mainly involved in cell adhesion, positive regulation of cell migration, and cytosol. The principal signaling pathways involved regulation of the actin cytoskeleton, vascular smooth contraction, and focal adhesion. The roles of these DEPs and associated signaling pathways serve as a fundamental framework for comprehending the mechanisms underpinning the onset and progression of TAO. Furthermore, we conducted a comprehensive evaluation of the effects of S100A8/A9 and its inhibitor, paquinimod, on smooth muscle cells (SMCs) and in TAO rats. We observed that paquinimod reduces SMCs proliferation and migration, promotes phenotype switching and alleviates vascular stenosis in TAO rats. In conclusion, our study revealed that the early activation of S100A8/A9 in the femoral artery is implicated in TAO development, targeting S100A8/A9 signaling may provide a novel approach for TAO prevention and treatment.

Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4.

Adjuvant chemoradiotherapy, molecular targeted therapy, and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer (GC). However, most of these treatments have toxic side effects, drug resistance, and limited improvements in survival and quality of life. Therefore, it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity. In previous studies, the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity; however, the specific mechanism was unclear. Our research utilising co-immunoprecipitation-mass spectrometry (Co-IP-MS), polypyrimidine tract binding protein 1 (ptbp1) clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9)-knockout (KO) mouse model, tissue microarray, and functional experiments suggests that alpha actinin-4 (ACTN4) could be a significant biomarker of GC. PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4. Celastrus orbiculatus stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.

Commensal microbe regulation of skin cells in disease.

Human skin is the host to various commensal microbes that constitute a substantial microbial community. The reciprocal communication between these microbial inhabitants and host cells upholds both the morphological and functional attributes of the skin layers, contributing indispensably to microenvironmental and tissue homeostasis. Thus, disruption of the skin barrier or imbalances in the microbial communities can exert profound effects on the behavior of host cells. This influence, mediated by the microbes themselves or their metabolites, manifests in diverse outcomes. In this review, we examine existing knowledge to provide insight into the nuanced behavior exhibited by the microbiota on skin cells in health and disease states. These interactions provide insight into potential cellular targets for future microbiota-based therapies to prevent and treat skin disease.

Sorting Technology for Mesenchymal Stem Cells from a Single Tissue Source.

Mesenchymal stem cells (MSCs) are adult stem cells that can be obtained, enriched and proliferated in vitro. They owned enormous potential in fields like regenerative medicine, tissue engineering and immunomodulation. However, though isolated from the same origin, MSCs are still essentially heterogeneous cell populations with different phenotypes and functions. This heterogeneity of MSCs significantly affects their therapeutic efficacy and brings obstacles to scientific research. Thus, reliable sorting technology which can isolate or purify MSC subpopulations with various potential and differentiation pathways is urgently needed. This review summarized principles, application status and clinical implications for these sorting methods, aiming at improving the understanding of MSC heterogeneity as well as providing fresh perspectives for subsequent clinical applications.