Home-based vs center-based exercise on patient-reported and performance-based outcomes for knee osteoarthritis: a systematic review with meta-analysis.

Background: Home-based exercise (HBE) represents an alternative to increase the accessibility of rehabilitation programs and relieve the burden on the health care system for people with knee osteoarthritis. Objectives: To summarize for the first time the effectiveness of HBE as compared to center-based exercise (CBE), both with and without HBE, on patient-reported and performance-based outcomes in people with KOA. Methods: Searches were conducted on PubMed, Cochrane, Embase, Web of Science, and Scopus until March 10, 2023, without date or language restrictions. Randomized controlled trials investigating HBE versus CBE or HBE combined with CBE for people with KOA were eligible. The primary outcomes were patient-reported: pain, physical disability, and quality of life. The secondary outcomes were performance-based: walking ability, lower limb muscle strength, and balance function. Risk of bias was assessed with the Cochrane Risk of Bias tool and quality of evidence according to the GRADE. Results: Eleven trials involving 956 participants were included. There was no difference in short-term pain (SMD, 0.22 [95% CI, -0.04 to 0.47], p = 0.09; I2 = 0%), physical disability (SMD, 0.17 [95% CI, -0.19 to 0.54], p = 0.35; I2 = 0%), walking ability (SMD, -0.21 [95% CI, -0.64 to 0.22], p = 0.33; I2 = 35%) and lower limb muscle strength (SMD, -0.24 [95% CI, -0.88 to 0.41], p = 0.47; I2 = 69%) between HBE and CBE. HBE combined with CBE has better benefits compared with HBE alone in short-term pain (SMD, 0.89 [95% CI, 0.60 to 1.17], p < 0.001; I2 = 11%) and physical disability (SMD, 0.25 [95% CI, 0.00 to 0.50], p = 0.05; I2 = 0%). Conclusion: Based on limited evidence, HBE is as effective as CBE on short-term pain, physical disability, walking ability, and lower limb muscle strength in people with knee osteoarthritis. Furthermore, combining HBE with CBE may enhance the overall efficacy of the intervention. Systematic review registration: PROSPERO, CRD42023416548.

The Effectiveness of Exercise-based Rehabilitation in People with Hand Osteoarthritis: A Systematic Review with Meta-analysis.

OBJECTIVE: To investigate the effectiveness of exercise-based rehabilitation programs compared with non-exercise intervention or no intervention for people with hand osteoarthritis (OA). DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched five databases on 23/07/2023. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared the effectiveness of rehabilitation programs that included an exercise component, with non-exercise intervention or no intervention for people with hand OA. DATA SYNTHESIS: Standardized mean differences (SMD) were pooled using a random effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. The certainty of the evidence was evaluated using the GRADE approach. RESULTS: Fourteen trials were included in the meta-analysis (n = 1341 participants). In the immediate-term (<24 weeks) there was low-certainty evidence of an effect of exercise-based rehabilitation on improving pain (13 trials; SMD -0.65, 95%CI: -1.06, -0.25), function (11 trials; SMD -0.35, 95%CI: -0.54, -0.15), and grip strength (14 trials; SMD 0.21, 95%CI: 0.03, 0.38). There was moderate-certainty evidence of an effect on reducing stiffness (7 trials; SMD -0.33, 95%CI: -0.51, -0.16). There was low-certainty evidence of no effect on improving pinch strength and quality of life. For the long-term ⩾24 weeks), there was low-certainty evidence that exercise-based rehabilitation had no additional effect on improving pain, function, and stiffness. CONCLUSION: Exercise-based rehabilitation improved pain, function, stiffness, and grip strength in people with hand OA in the immediate-term; the benefits were not maintained in the long-term.

Parallel-Forms Reliability and Minimal Detectable Change of the Four Telerehabilitation Version Mobility-Related Function Scales in Stroke Survivors.

OBJECTIVE: To investigate the parallel-forms reliability, minimal detectable change with 95% confidence interval (MDC95), and feasibility of the 4 telerehabilitation version mobility-related function scales: Fugl-Meyer Assessment-lower extremity subscale (Tele-FMA-LE), Berg Balance Scale (Tele-BBS), Tinetti Performance Oriented Mobility Assessment-Gait subscale (Tele-POMA-G), and Rivermead Mobility Index (Tele-RMI). DESIGN: Reliability and agreement study and cross-sectional study. SETTING: Medical center. PARTICIPANTS: Stroke survivors' ability to independently walk 3 meters with assistive devices, age of ≥18 years for participants and their partners, stable physical condition, and absence of cognitive impairment (N=60). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Parallel-forms reliability and MDC95 of Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI. RESULTS: No significant differences (P>.05) were observed among the mean scores of the telerehabilitation version and face-to-face version mobility-related function scales. Intraclass correlation coefficients (ICCs) indicated good reliability for most scales, with Tele-FMA-LE, Tele-BBS, and Tele-RMI scores achieving values of 0.81, 0.78, and 0.84. Tele-POMA-G scores demonstrated moderate reliability (ICC=0.72). Weighted kappa (κw) showed good-to-excellent reliability for most individual items (κw>0.60). The MDCs of the Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI were 5.84, 8.10, 2.74, and 1.31, respectively. Bland-Altman analysis showed adequate agreement between tele-assessment and face-to-face assessment for all scales. The 5 dimensions affirm the robust feasibility of tele-assessment: assessment time, subjective fatigue perception, overall preference, participant satisfaction, and system usability. CONCLUSIONS: The study demonstrates good parallel-forms reliability, MDC, and promising feasibility of the 4 telerehabilitation version mobility-related function scales (Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI) in survivors of stroke.

Steering CO2 Electroreduction to C2+ Products via Enhancing Localized *CO Coverage and Local Pressure in Conical Cavity.

The electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) involves a multistep proton-coupled electron transfer (PCET) process that generates a variety of intermediates, making it challenging to transform them into target products with high activity and selectivity. Here, a catalyst featuring a nanosheet-stacked sphere structure with numerous open and deep conical cavities (OD-CCs) is reported. Under the guidance of the finite-element method (FEM) simulations and theoretical analysis, it is shown that exerting control over the confinement space results in diffusion limitation of the carbon intermediates, thereby increasing local pressure and subsequently enhancing localized *CO coverage for dimerization. The nanocavities exhibit a structure-driven shift in selectivity of multicarbon (C2+) product from 41.8% to 81.7% during the CO2RR process.

Most of the pelvic floor muscle functions in women differ in different body positions, yet others remain similar: systematic review with meta-analysis.

Objectives: This systematic literature review and meta-analysis aimed to determine the effect of body position on the measurement of pelvic floor muscle (PFM) contractility and to analyze the influential factors. Data sources: Five databases (PubMed, Web of Science, EMBASE, Cochrane Library and Scopus) were searched for relevant studies published up to 12nd October 2023. Study selection or eligibility criteria: Included cross-sectional studies had to involve the assessment of pelvic floor muscle function in at least two positions. Study appraisal and synthesis methods: We calculated standardized mean difference (SMD) with 95% confidence intervals (CI) to ascertain the potential effect of body position on outcomes. Results: In total, we included 11 cross-sectional studies to ascertain the potential effect of body position on outcomes. There was no statistical difference in the results of maximum voluntary contraction (MVC) of the pelvic floor muscles when assessed in between supine and standing positions (SMD -0.22; 95% CI -0.72 to 0.28; p = 0.38). The results of the meta-analysis showed significantly larger values of resting voluntary contractions (RVC) measured in the standing position compared to the supine position (SMD -1.76; 95% CI -2.55 to -0.97; p < 0.001). Moreover, pelvic floor muscle movement during pelvic floor muscle contraction in the standing position was significantly better than that measured in the supine position (SMD -0.47; 95% CI -0.73 to 0.20; P < 0.001). Conclusion: The results of this study showed that the RVC and PFM movement varied with the position of the assessment. In contrast, MVC values are independent of the assessment position and can be selected according to clinical needs. Systematic review registration: PROSPERO, identifier CRD42022363734, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022363734.

The critical role of platelet in cancer progression and metastasis.

Platelets play a crucial role in cancer blood metastasis. Various cancer-related factors such as Toll-like receptors (TLRs), adenosine diphosphate (ADP) or extracellular matrix (ECM) can activate these small particles that function in hemostasis and thrombosis. Moreover, platelets induce Epithelial Mesenchymal Transition (EMT) to promote cancer progression and invasiveness. The activated platelets protect circulating tumor cells from immune surveillance and anoikis. They also mediate tumor cell arrest, extravasation and angiogenesis in distant organs through direct or indirect modulation, creating a metastatic microenvironment. This review summarizes the recent advances and progress of mechanisms in platelet activation and its interaction with cancer cells in metastasis.

Can we trust computers to assess the cognition of stroke patients? A systematic review.

Purpose: To summarize the classification of computerized cognitive assessment (CCA) tools for assessing stroke patients, to clarify their benefits and limitations, and to reveal strategies for future studies on CCA tools. Methods: A literature review was performed using PubMed, Embase, Scopus, JAMA Network, Cochrane Library and PsycINFO databases from January 1st, 2010, to August 1st, 2022. Two authors independently screened the literature following the same criteria, evaluated the study quality, and collected data from the articles. Results: A total of 8,697 papers were acquired from the six databases. A total of 74 potentially eligible articles were selected for review. Of these, 29 articles were not relevant to this research, 3 were reviews, 2 were not written in English, and 1 was on an ongoing trial. By screening the references of the reviews, 3 additional articles were included in this study. Thus, a total of 42 articles met the criteria for the review. In terms of the CCA tools analyzed in these studies, they included five types: virtual reality (VR)-based, robot-based, telephone-based, smartphone-based, and computer-based cognitive assessments. Patients' stages of the disease ranged from the subacute phase and rehabilitation phase to the community phase. A total of 27 studies supported the effectiveness of CCA tools, while 22 out of 42 articles mentioned their benefits and 32 revealed areas for future improvement of CCA tools. Conclusions: Although the use of CCA tools for assessing the cognition of post-stroke patients is becoming popular, there are still some limitations and challenges of using such tools in stroke survivors. More evidence is thus needed to verify the value and specific role of these tools in assessing the cognitive impairment of stroke patients.

Exploration of KIR genes and hematological-related diseases in Chinese Han population.

The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41-0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58-0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.

A single dose of lipopolysaccharide elicits autofluorescence in the mouse brain.

One hallmark of aging is autofluorescence (AF) in the brain. However, the underlying mechanism for inducing AF remains unknown. This study aims to determine the cause(s) of this phenomenon. The endogenous expression pattern of AF in mice was examined at differing ages. Intraperitoneal injection of a single dose of lipopolysaccharide (LPS) was performed to induce AF. Copper sulfate was applied to remove AF to allow for further immunofluorescence staining. AF appeared in the mouse brain as early as 3 months of age. In the cortex, AF occurs in the lysosomes of microglia, astrocytes, endothelial cells, and oligodendrocyte lineage cells and its prevalence increases with age. Interestingly, AF never occurs in the pericytes of young or aged brains. LPS administration resulted in a rapid and marked induction of brain AF, similar to the normal aging process. Finally, age-related and induced AF can be eliminated by low concentrations of copper sulfate solution. This pre-treatment is safe for aging and lineage tracing studies. These findings depict that AF in the brain could be associated with the innate immune response against Gram-negative bacteria infection.

Predicting of motor vehicle carbon emissions and spatio-temporal characteristic analysis in the Beijing-Tianjin-Hebei region.

In China, road traffic carbon emissions and their share in total carbon emissions have significantly increased. In the context of double carbon, the Beijing-Tianjin-Hebei region, the largest urban agglomeration in northern China, is receiving more and more attention. Due to the unbalanced development in Beijing-Tianjin-Hebei urban agglomeration, this thesis presents three computational models to calculate road traffic carbon emissions for large, medium-sized, and small cities and intercity traffic arteries based on the road network. The results show that in 2019, Beijing has the highest road carbon emissions reaching 19.91 million t CO2 which is almost three times that of Shijiazhuang, the capital city of Hebei province. Dwellers' commuting usually results in an increase of 2.9%, 3.3%, and 4.5% on weekdays compared with weekends for Tianjin, Shijiazhuang, and Beijing, respectively. As for the intercity road, the daily traffic flow is about 1.92 million vehicles, leading to total carbon emissions of 22.97 million t CO2. In addition, the reduction potential of carbon emissions in Beijing is evaluated. If the average road speed is increased to 0.9Vf (road design speed) during the morning rush hour in Beijing from 7 a.m. to 8 a.m., the road emission reduction could reach 57.85%.

Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma.

Glutamine metabolism is critical both for the proliferation of cancer cells and the activation of CD8T cells to kill cancer cells. We aim to explore the relationship between the glutamine metabolism of CD8T cells and cancer cells and tumor immunity in the tumor microenvironment. In a TCGA cohort, we found that patients with high scores of glutamine-metabolism-related genes showed poor prognoses, and that a high score of glutamine-metabolism-related genes was an independent risk factor for HCC patients. In single-cell RNA-seq data, we found that, in some patients, the glutamine metabolism gene scores of tumor cells were significantly higher than those of CD8T cells, while decreased ratios of CD8-Tef-GZMA and suppressed tumor-killing activity of CD8-Tef-APOC2 were observed. A further genetic dynamics pseudotime analysis suggested that immune remodeling of these two subpopulations was accompanied by metabolic reprogramming. CD8-Tef-APOC2 in the dominant group tended to metabolize exogenous lipids, while the metabolic program of CD8-Tef-GZMA in the nondominant group was characterized by amino acid and endogenous lipid synthesis. In addition, we found that the glutamine metabolism inhibitor JHU083 promoted the proliferation of CD8T cells and improved the efficacy of PD-1 blockers. We proposed a new tool to quantify the glutamine partitioning between tumor cells and CD8T cells, through which the unique immune microenvironment could be identified at the transcriptome level. Furthermore, the simultaneous destruction of the glutamine metabolism in tumor cells and CD8T cells facilitated the enrichment of tumor-infiltrating CD8T cells and enhanced the efficacy of immunotherapy.

Successful application of indocyanine green fluorescent imaging for the non-invasive detection of postoperative bile leakage.

There is a lack of a simple and reliable method for the diagnosis of postoperative bile leakage. ICG is a water-soluble fluorescent contrast agent. After intravenous injection of ICG, ICG is eventually excreted only through the biliary tract system into the intestines. It is highly sensitive, stable and nonradioactive, and these characteristics provide a theoretical basis for using ICG to diagnose postoperative bile leakage. Two patients with postoperative bile leakage were successfully identified using indocyanine green fluorescent imaging for the first time, suggesting its potential to be a convenient and reliable method for the diagnosis of postoperative bile leakage.

Digital Rehabilitation Programs Improve Therapeutic Exercise Adherence for Patients With Musculoskeletal Conditions: A Systematic Review With Meta-Analysis.

OBJECTIVE: To investigate the effects of digital rehabilitation for improving adherence to therapeutic exercise in people with musculoskeletal conditions. DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: Five databases were searched from their inception to March 2022. STUDY SELECTION CRITERIA: We included randomized controlled trials evaluating digital rehabilitation programs to improve adherence to therapeutic exercise for people with musculoskeletal conditions. DATA SYNTHESIS: We calculated standardized mean differences (SMDs) or mean differences (MDs) and 95% confidence intervals (CIs). Certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Bias was assessed using the Cochrane risk of bias tool. RESULTS: Eleven trials were included in the meta-analysis (n = 1144 participants). At short-term follow-up, digital rehabilitation was no better than nondigital rehabilitation (3 trials, adherence rate of prescribed exercise test SMD 0.50, 95% CI: -0.13, 1.13; 2 trials, self-reported exercise adherence test MD 1.07, 95% CI: 0.58, 1.56; 2 trials, assessor-reported exercise adherence test SMD -0.10, 95% CI: -0.56, 0.36). At intermediate-term follow-up, digital rehabilitation improved exercise adherence compared with nondigital rehabilitation (6 trials, adherence rate of prescribed exercise test SMD 0.53, 95% CI: 0.35, 0.70; 2 trials, self-reported exercise adherence test MD 1.50, 95% CI: 0.76, 2.25; 2 trials, Exercise Adherence Rating Scale test MD 5.86, 95% CI: 0.08, 11.65). At long-term follow-up, there was no clinically important difference between digital and nondigital rehabilitation (2 trials, adherence rate of prescribed exercise test SMD 0.28, 95% CI: -0.14, 0.70; 1 trial, self-reported exercise adherence test MD 0.20, 95% CI: -0.91, 1.31). CONCLUSION: Digital rehabilitation was effective at improving therapeutic exercise adherence in musculoskeletal conditions at mid-term follow-up, but not at short- and long-term follow-up. J Orthop Sports Phys Ther 2022;52(11):726-739. Epub: 12 August 2022. doi:10.2519/jospt.2022.11384.

Alcohol Extract of YFXJ Decoction Reverses the Drug Resistance of Human Lung Adenocarcinoma Cell Line A549/DDP.

Objective: Lung cancer is the wide and common tumor. This study was designed to explore the effect of YFXJ formula on non-small-cell lung cancer (NSCLC) cell lines. Methods: YFXJ formula (mainly composed of Astragalus membranaceus, Atractylodes macrocephala, Radix Saposhnikoviae, Radix Glehniae, coix seed, Herba Sabina chinensis, Hedyotis diffusa, Pericarpium Citri Reticulatae, sarcophagus martensii, Prunella vulgaris, Meretrix meretrix, and oyster) was extracted with 75% ethanol. We performed MTT, FACS, TUNEL, and mass spectrometry to study the effect of YFXJ formula on A549/DDP cells. Results: The results showed that YFXJ could inhibit the growth of A549/DDP cells, and it can reverse the sensitivity of A549/DDP cells to cisplatin. YFXJ inhibits the expression of MDR1, MRP1, and LRP genes in A549/DDP cells. Conclusion: YFXJ formula can reverse the drug resistance of A549/DDP cell, which could be through activation of autophagy.

Sexual Dysfunction After Traumatic Injury Can Be Corrected by Transcranial Magnetic Stimulation: A Case Report.

Neurogenic sexual dysfunction (NSD) is a common problem in patients after spinal and pelvic trauma. New treatment is needed beyond medicine or psychological therapies. A 24-year-old man who fell from a six-floor building suffered from subsequent NSD. Repetitive transcranial magnetic stimulation (rTMS) was the only method used to treat his NSD caused by multiple spinal and pelvic injuries. The therapy lasted for 3 courses. Motor and sensory conduction, as well as sexual function, were evaluated before and after the rTMS intervention. Improvements on patient's nerve conduction and sexual activity were confirmed at a 1-year follow-up. Our findings indicate that rTMS delivered a novel, positive and low-cost modality treatment to the patient with NSD. Clinical efficacy and potential mechanisms by which rTMS regulate NSD need to be investigated by further clinical trials.

Protective mechanism of traditional Chinese medicine guizhi fuling pills against carbon tetrachloride-induced kidney damage is through inhibiting oxidative stress, inflammation and regulating the intestinal flora.

BACKGROUND: Chemical or drug-induced kidney damage has been recognized as a critical cause of kidney failure. The oxidative stress, inflammation, and imbalance of intestinal flora caused by carbon tetrachloride (CCl4) play a fundamental role in chronic kidney damage. Guizhi Fuling pills (GZFL) is a traditional formula consisting of five traditional Chinese medicinal herbs, which can promote blood circulation and improve kidney function. The underlying mechanisms of GZFL improving kidney damage are not fully understood yet. AIM: The current study aimed to explore the effects of GZFL on CCl4-induced kidney damage and intestinal microbiota in mice. METHODS: Male ICR mice were intraperitoneally administered with 20% CCl4 (mixed in a ratio of 1:4 in soybean oil) twice a week, for 4 weeks to induce kidney damage. Creatinine (CRE), urea nitrogen, antioxidant enzymes, and inflammatory cytokines were measured and the histology of the kidney, jejunum, and colon examination to assess kidney and intestinal damage. The expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) family members, nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in kidney tissues, and the tight junction proteins in colonic tissues were detected by Western blot. The gut microbiota was analyzed through 16S rRNA gene sequencing. RESULTS: GZFL treatment decreased the serum CRE and urea nitrogen levels. Moreover, GZFL reduced the levels of pro-inflammatory cytokines and increased antioxidant enzyme activities in kidney and colonic tissues. GZFL improved the kidney, jejunum, and colon histology. Furthermore, GZFL inhibited the expressions of NLRP3, ASC, and cleaved-Caspase-1, while Nrf2, HO-1, NQO1, GCLM, and tight junction proteins were increased. The dysbiosis of intestinal microbiota improved after GZFL treatment. CONCLUSIONS: This study showed that GZFL could improve kidney damage, which might be mainly via the integrated regulations of the Nrf2 pathway, NLRP3 inflammasome, and composition of intestinal microbiota.

Pediatric Continuous Reference Intervals of Serum Insulin-like Growth Factor 1 Levels in a Healthy Chinese Children Population - Based on PRINCE Study.

OBJECTIVES: We aimed to establish age- and sex-dependent reference intervals for insulin-like growth factor 1 (IGF-1) based on the measurements of healthy Chinese children from the pediatric reference intervals in China study and to investigate whether body mass index (BMI) and height affect IGF-1 levels. METHODS: A total of 3753 individuals with eligible blood specimens resampled from the pediatric reference intervals in China population were enrolled as reference individuals. IGF-1 levels were measured using a chemiluminescent immunoassay kit. The lower limit and upper limit values of the reference individuals were calculated by defining the 2.5th and 97.5th percentiles. The skewness-median-coefficient of variation method was used to calculate the standard deviation score (SDS) of serum IGF-1, and cubic spline curves were applied to depict a smoothed curve for each age- and sex-specific stratification of the L, M, and S parameters. RESULTS: Serum IGF-1 levels increased with age from the age of 1 year, peaking at around the age of 13 years in girls and 15 years in boys and then began to decline (both P <.001). Before 14 years, IGF-1 levels were higher in girls than in boys at the same age, and the difference was statistically significant (P < .05), but there was no significant difference in the IGF-1 levels between girls and boys aged 14 to 16 and 18 years. The Spearman correlation coefficients of height SDS, weight SDS, and BMI SDS with IGF-1 SDS were 0.29, 0.33, and 0.20, respectively (P < .001). CONCLUSION: This study established age- and sex-specific normative IGF-1 data for Chinese children and adolescents between the ages of 1 and 19 years. The BMI and height SDS had no effect on IGF-1 levels in healthy children.

Guizhi Fuling pill attenuates liver fibrosis in vitro and in vivo via inhibiting TGF-ß1/Smad2/3 and activating IFN-γ/Smad7 signaling pathways.

Liver fibrosis resulting from chronic liver injuries (CLI) is a common health problem globally. Guizhi Fuling pill (GZFL), a modern preparation from traditional Chinese medicine, exhibited anti-dysmenorrhea, anti-inflammatory, and immune-regulative effects. However, the effect of GZFL on liver fibrosis remains unknown. In this research, LX-2 cells were stimulated with acetaldehyde for mimicking liver fibrosis progression in vitro. In addition, carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was established as well. The data revealed GZFL obviously suppressed the proliferation and triggered the apoptosis of acetaldehyde-stimulated LX-2 cells. In addition, GZFL prevented acetaldehyde-induced activation of LX-2 cells via downregulation of TGF-ß1, p-Smad2, p-Smad3, CUGBP1, and upregulation of p-STAT1 and Smad7. Meanwhile, GZFL significantly alleviated CCl4­induced liver fibrosis, as evidenced by the decrease of ALT and AST levels. Moreover, GZFL downregulated the expressions of TGF-ß1, p-Smad2, p-Smad3, and CUGBP1 in CCl4-treated mice. Furthermore, GZFL remarkably elevated the levels of IFN-γ, p-STAT1, and Smad7 in CCl4-treated mice. To sum up, GZFL was able to inhibit liver fibrosis in vitro and in vivo through suppressing TGF-ß1/Smad2/3-CUGBP1 signaling and activating IFN-γ/STAT1/Smad7 signaling. Thus, GZFL might have a potential to act as a therapeutic agent for anti-fibrotic therapy.

Analysis of the microRNA and mRNA expression profile of ricin toxin-treated RAW264.7 cells reveals that miR-155-3p suppresses cell inflammation by targeting GAB2.

Ricin toxin (RT) is one of the most lethal toxins derived from the seed of castor beans. In addition to its main toxic mechanism of inhibiting the synthesis of cellular proteins, RT can induce the production of inflammatory cytokines. MicroRNAs (miRNAs) play a key role in regulating both innate and adaptive immunity. To elucidate the regulation of miRNAs in RT-induced inflammation injury, the RNA high-throughput sequencing (RNA-Seq) technology was used to analyze the expression profile of miRNAs and mRNAs in RT-treated RAW264.7 cells. Results showed that a total of 323 mRNAs and 19 miRNAs differentially expressed after RT treated. Meanwhile, 713 miRNA-mRNA interaction pairs were identified by bioinformatics analysis. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that those interaction pairs were mainly involved in JAK-STAT, T cell receptor, and MAPK signaling pathways. Moreover, we further predicted and determined the targeting relationship between miR-155-3p and GAB2 through TargetScan and dual-luciferase reporter assay. Mechanically, overexpression of miR-155-3p can reduce the secretion of TNF-α in RAW264.7 cells, revealing a possible mechanism of miR-155-3p regulating RT-induced inflammatory injury. This study provides a new perspective for clarifying the mechanism of RT-induced inflammatory injury and reveals the potential role of miRNAs in innate immune regulation.

Mapping germ-layer specification preventing genes in hPSCs via genome-scale CRISPR screening.

Understanding the biological processes that determine the entry of three germ layers of human pluripotent stem cells (hPSCs) is a central question in developmental and stem cell biology. Here, we genetically engineered hPSCs with the germ layer reporter and inducible CRISPR/Cas9 knockout system, and a genome-scale screening was performed to define pathways restricting germ layer specification. Genes clustered in the key biological processes, including embryonic development, mRNA processing, metabolism, and epigenetic regulation, were centered in the governance of pluripotency and lineage development. Other than typical pluripotent transcription factors and signaling molecules, loss of function of mesendodermal specifiers resulted in advanced neuroectodermal differentiation, given their inter-germ layer antagonizing effect. Regarding the epigenetic superfamily, microRNAs enriched in hPSCs showed clear germ layer-targeting specificity. The cholesterol synthesis pathway maintained hPSCs via retardation of neuroectoderm specification. Thus, in this study, we identified a full landscape of genetic wiring and biological processes that control hPSC self-renewal and trilineage specification.