Synergistic Sr Activation and Cr Buffering Effect on RuO2 Electronic Structures for Enhancing the Acidic Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of ruthenium-based oxides strongly correlates with the electronic structures of Ru. However, the widely adopted monometal doping method unidirectionally regulates only the electronic structures, often failing to balance the activity and stability. Here, we propose an "elastic electron transfer" strategy to achieve bidirectional optimization of the electronic structures of Sr, Cr codoped RuO2 catalysts for acidic OER. The introduction of electron-withdrawing Sr intrinsically activates the Ru sites by increasing the oxidation state of Ru. Simultaneously, Cr acts as an electron buffer, donating electrons to Ru in the presence of Sr in the as-prepared catalysts and absorbing excess electrons from Sr leaching during the OER. Such a bidirectional regulation feature of Cr prevents overoxidation of Ru and maintains its high oxidation state during the OER. The optimal Ru3Cr1Sr0.175 catalyst exhibits a low overpotential (214 mV @ 10 mA cm-2) and excellent stability (over 300 h).

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.

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.

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.

High Expression of CARM1 Inhibits Lung Cancer Progression by Targeting TP53 by Regulating CTNNB1.

OBJECTIVE: To explore the role of CARM1 in lung cancer (LC) and its relationship with TP53 and CTNNB1. METHODS: Lung cells H1299 and PC14 were randomly divided into six groups: ov-H1299, si-H1299, ov-PC14, si-PC14, Con-H1299, and Con-PC14. Transwell assay, plate clone formation assay, and flow cytometry were used to determine the migration, clone formation capacity, and apoptosis situation of LC cells in the six groups, respectively. Western blot assay was used to determine the protein expression of CARM1, TP53, and CTNNB1 in the six groups. CHIP assay was applied to analyze the combined characteristics of JUN and TP53 promoter. Co-immunoprecipitation was used to analyze the interaction between TP53 and CARM1/CTNNB1. Cox proportional hazard regression model was used to analyze the relevance between the expression of CARM1 and clinicopathological information of the patient. Kaplan-Meier plot was used to determine the relevance between CARM1 and patient survival. RESULTS: High expression of CARM1 inhibits the migration and proliferation of LC cells and promoted the apoptosis of LC cell. Overexpression of CARM1 promotes the expression of CARM1 and TP53, while decreases CTNNB1 expression. CARM1 supplementation of H1299 cells induced JUN aggregation on the TP53 promoter. TP53 and CARM1 protein/TP53 and CTNNB1 protein in H1299 cells were immunoprecipitated together. High expression of CARM1was negatively correlated with the degree of tumor metastasis. The survival period of patients with high expression CARM1 was greater than that of low expression. CONCLUSION: Overexpression of CARM1 may inhibit the progression of LC by targeting TP53 via regulation CTNNB1.

The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model.

The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.

Combined application of diclofenac and celecoxib with an opioid yields superior efficacy in metastatic bone cancer pain: a randomized controlled trial.

BACKGROUND: Metastatic bone cancer pain is one of the most common clinical cancer pains and is caused by many factors. This study was conducted to explore the clinical efficacy of using two non-steroidal anti-inflammatory drugs (NSAIDs) along with an opioid in treating metastatic bone cancer pain. MATERIAL AND METHOD: A total of 342 patients with a pain score of 7-10 on the visual analog scale (VAS) were recruited for 4 weeks of treatment and randomly assigned to three different groups-one group received two NSAIDs (diclofenac and celecoxib), one group received diclofenac, and one group received celecoxib. All patients received morphine sulfate 10 mg/12 h with a reduction of 50% or addition of 25% each time until the VAS score was <5. The VAS score, remission rate (RR), breakthrough pain (BTP), morphine sulfate dose and side-effects among the three groups were compared. RESULTS: After 4 weeks of treatment, we found that using two NSAIDs along with an opioid could yield a significantly lower VAS score (p = 0.006), higher RR (p = 0.0002) and fewer incidences of BTP (p = 0.011), compared to the use of only one NSAID. Furthermore, using two NSAIDS could significantly decrease the consumption of morphine sulfate compared to using each NSAID in isolation (p = 0.0031 in week 1; p = 0.020 in week 2; p = 0.0012 in week 4). Additionally, using two NSAIDs could produce fewer incidences of dizziness (p = 0.002), constipation (p < 0.0001) and drowsiness (p < 0.0001). CONCLUSION: Although limited by the relatively small samples, these results indicate that using two NSAIDs along with an opioid in treating metastatic bone cancer pain was more effective and acceptable, which is worthy of further clinical application.

A comparative study of graphene-coated stainless steel fiber felt and carbon cloth as anodes in MFCs.

This study investigated the stainless steel-based materials and their potential in microbial fuel cells (MFCs) anode application. Herein, AISI 316L stainless steel fiber felts (SSFFs) were used as anodes in MFCs and their performance was compared with the carbon cloth anode MFCs. The experimental results showed that the unmodified carbon cloth (CC) anode had a better performance than the unmodified SSFF anode. However, after coating a thin layer of graphene (GN) on SSFF and CC, the power density of the MFC equipped with the modified SSFF was 2,143 mW m(-2), much higher than that of the graphene-modified CC-MFC which was only 1,018 mW m(-2). The experimental results proved that the use of durable metallic backbones combined with a thin layer of carbon nanoparticles offers exciting opportunities in the advancement of MFC anode design.

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 nonexercise intervention or no intervention for people with hand osteoarthritis (OA). DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched 5 databases on July 23, 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared the effectiveness of rehabilitation programs that included an exercise component, with nonexercise intervention or no intervention for people with hand OA. DATA SYNTHESIS: Standardized mean differences (SMDs) 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 Grading of Recommendations, Assessment, Development, and Evaluations (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. J Orthop Sports Phys Ther 2024;54(7):1-11. Epub 20 March 2024. doi:10.2519/jospt.2024.12241.

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.

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.

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.

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%.

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.

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.

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.

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.

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.

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.

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.