The mediating effects of self-efficacy and study engagement on the relationship between specialty identity and career maturity of Chinese nursing students: a cross-sectional study.

BACKGROUND: Career maturity is a crucial indicator of career preparedness and unpreparedness can cause the turnover of new nurses. Considerable empirical work demonstrates the potential associations between specialty identity, self-efficacy, study engagement, and career maturity. This study aimed to explore the mediation role of self-efficacy and study engagement on the relationships between specialty identity and career maturity among Chinese nursing students. METHODS: Four hundred twenty-six Chinese nursing students were recruited between September 11 and October 30, 2022. The online survey was conducted following the CHERRIES checklist. Electronic questionnaires assessed their perceived specialty identity, self-efficacy, study engagement, and career maturity. The descriptive analysis, Harman single-factor analysis, Pearson correlation tests, structural equation modeling, and the bootstrap method were employed in data analysis. RESULTS: Bivariate correlation analysis identified a positive correlation between specialty identity, self-efficacy, study engagement, and career maturity (r = 0.276-0.440, P < 0.001). Self-efficacy and study engagement partially mediated the relationship between specialty identity and career maturity. Self-efficacy and study engagement played a chain mediating role between specialty identity and career maturity. CONCLUSIONS: The underlying mechanism can explain the relationships between specialty identity and career maturity: a direct predictor and an indirect effect through self-efficacy and study engagement. Policymakers and educators should emphasize the importance of specialty identity and provide tailored strategies for improving care maturity depending on nursing students' specialty identity, self-efficacy, study engagement in the early stages of career development.

Exposure to low-dose cadmium induces testicular ferroptosis.

As an environmental pollutant, cadmium (Cd) has been widely reported to induce male infertility due to its gonadotoxicity. However, the specific mechanism of Cd-induced testicular damage remains unclear. We investigated whether Cd causes testicular injury through ferroptosis. Male C57BL/6 J mice were exposed to 0, 0.5, or 5 ppm Cd via drinking water, starting in utero, and continuing through 24 weeks post-weaning. The results showed that Cd accumulated in the testes in a dose-dependent manner. Cd exposure at a concentration of 5 ppm, but not 0.5 ppm, caused a mass loss and detachment of germ cells, as well as a decreased meiotic index and testis weight. Exposure to 5 ppm Cd caused iron accumulation, increased levels of malondialdehyde (MDA) and nitro tyrosine (3-NT), and decreased expression of Nrf2, HO-1 and SOD2. We also found that exposure to 5 ppm Cd significantly decreased the expression of SLC7A11, a marker of ferroptosis in mice, along with the expression of SLC40A1 mRNA and ferritin heavy chain (FTH) protein, whereas there was no obvious change in the mRNA expression of Tfrc, ZIP8, ZIP14, and NCOA4. These findings indicate that 5 ppm Cd exposure increased testicular ferroptosis, which may be attributed to the reduction of stored iron export.

Nurse-to-nurse horizontal violence in Chinese hospitals and the protective role of head nurse's caring and nurses' group behaviour on it: A cross-sectional study.

AIMS: This study aimed to analyse the prevalence of nurse-to-nurse horizontal violence in Chinese hospitals and examine the effects of head nurse's caring and nurse's group behaviour on horizontal violence. BACKGROUND: Horizontal violence is a serious global problem affecting the nursing profession, but little is known of the issue in Chinese hospitals. Increasing evidence has showed that leadership and group factors are important in facilitating horizontal violence. Whether the head nurse's caring and group behaviour perceived by nurses has protective effects against horizontal violence remains unclear. METHODS: A cross-sectional online-based questionnaire study was performed in seven general hospitals in Hubei Province, China. Data related to the demographic information, horizontal violence, head nurse's caring and group behaviour were collected. Descriptive analyses, chi-squared tests and logistic regression were used for data analysis. RESULTS: In total, 1942 valid questionnaires were collected, with a 92.70% effective response rate (1942/2095). Of those, 59.1% (1148/1942) of respondents had experienced horizontal violence at least once in the previous 6 months. Covert negative behaviours were more frequently reported. Compared with the low level, moderate and high levels of the head nurse's caring showed a lower risk of horizontal violence (odds ratio [OR] = 0.400, p < .001; OR = 0.128, p < .001); moderate and high levels of group behaviour also showed a reduced risk (OR = 0.601, p < .001; OR = 0.221, p < .001). CONCLUSION: Horizontal violence is common among Chinese nurses. The head nurse's caring and maintaining a good climate of nurses' group behaviours could serve as protective factors for preventing horizontal violence. IMPLICATIONS FOR NURSING MANAGEMENT: This study helps nursing managers identify which specific negative behaviours occur frequently and require special attention. It suggests that nursing managers attach importance to improving their caring ability towards nurses and to creating an amicable climate of group behaviour to buffer against horizontal violence.

Chinese nurses' perceptions on toxic leadership behaviours of nurse managers: A qualitative study.

AIM: The aim of this study is to explore the perceptions of Chinese registered nurses on toxic leadership behaviours of nurse managers and to determine its type, cause and response measures. BACKGROUND: The nurse manager is the front-line leader of the nurses who provide services directly to patients. Previous evidence suggests that toxic leadership behaviours of nurse managers do exist and it is necessary to understand the specifics of it. METHODS: We used phenomenological research methods to conduct semi-structured in-depth interviews among 12 nurses at a tertiary hospital in Wuhan over the period from January to March 2022. And the data were analysed using Colaizzi seven-step analysis method. RESULTS: Four themes were discovered: (a) nurses' perceptions of toxic leadership behaviours; (b) toxic leadership behaviours of nurse managers; (c) reasons for toxic leadership behaviours of nurse managers and (d) measures for toxic leadership behaviours of nurse managers. CONCLUSION: Chinese nurses are exposed to the toxic leadership of nurse managers for multiple reasons and respond differently. IMPLICATIONS FOR NURSING MANAGEMENT: This study helps nursing managers identify which behaviours are harmful to the nurse that require special attention in developing strategies to buffer against nurse managers' toxic leadership.

Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study.

BACKGROUND: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China. METHODS: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate. RESULTS: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells. CONCLUSION: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.

Comprehensive Review of Cadmium Toxicity Mechanisms in Male Reproduction and Therapeutic Strategies.

Cadmium (Cd) has been widely studied as an environmental pollutant for many years. Numerous studies have reported that Cd exposure causes damage to the heart, liver, kidneys, and thyroid in vivo. The emerging evidence suggests that Cd exposure induces damage on male reproductive system, which is related to oxidative stress, inflammation, steroidogenesis disruption, and epigenetics. Current preclinical animal studies have confirmed a large number of proteins and intracellular signaling pathways involved in the pathological process of Cd-induced male reproductive damage and potential measures for prophylaxis and treatment, which primarily include antioxidants, anti-inflammatory agents, and essential ion supplement. However, explicit pathogenesis and effective treatments remain uncertain. This review collects data from the literatures, discusses the underlying mechanisms of Cd-induced toxicity on male reproductive function, and summarizes evidence that may provide guidance for the treatment and prevention of Cd-induced male reproductive toxicity.

Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2: A systematic review and meta-analysis.

BACKGROUND: Currently, the epidemic of coronavirus disease 2019 (COVID-19) has begun to spread worldwide. We aim to explore reliable evidence for the diagnosis and treatment of the COVID-19 by analyzing all the published studies by Chinese scholars on the clinical and imaging features in novel coronavirus pneumonia caused by SARS-CoV-2. METHODS: We searched five medical databases including two Chinese and three English databases for all published articles on COVID-19 since the outbreak. A random-effects model was designed, and the imaging and clinical data from all studies were collected for meta-analysis. RESULTS: Overall, 31 articles and 46 959 patients were included, including 10 English articles and 21 Chinese articles. The results of meta-analysis showed that the most common clinical manifestations were fever (87.3%; 0.838-0.909), cough (58.1%; 0.502-0.660), dyspnea (38.3%; 0.246-0.520), muscle soreness or fatigue (35.5%; 0.253-0.456), and chest distress (31.2%; -0.024 to 0.648). The main imaging findings were bilateral pneumonia (75.7%; 0.639-0.871) and ground-glass opacification (69.9%; 0.602-0.796). Among the patients, the incidence that required intensive care unit (ICU) was (29.3%; 0.190-0.395), the incidence with acute respiratory distress syndrome was (28.8%; 0.147-0.429), the incidence with multiple organ dysfunction syndrome was (8.5%; -0.008 to 0.179), and the case fatality rate of patients with COVID-19 was (6.8%; 0.044-0.093). CONCLUSION: COVID-19 is a new clinical infectious disease that mainly causes bilateral pneumonia and lung function deteriorates rapidly. Nearly a third of patients need to be admitted to the ICU, and patients are likely to present respiratory failure or even death.

Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists.

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).

Synthesis and evaluation of novel fused pyrimidine derivatives as GPR119 agonists.

A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16, 19, 26, 28, 42) bearing endo-N-Boc-nortropane amine and fluoro-substituted aniline exhibited better EC50 values (0.27-1.2 µM) though they appeared to be partial agonists.

Design and synthesis of novel pyrimido[5,4-d]pyrimidine derivatives as GPR119 agonist for treatment of type 2 diabetes.

We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activities with single digit EC50 values (2.2 nM and 8.1 nM, respectively). Therefore, 15a and 21e were evaluated for their oral glucose tolerance test (oGTT) in C57BL/6N mice. Compound 15a reduced the blood glucose area of under curve from 0 to 2 h (AUC0-2h) to 13.5% at the dose of 15 mg/kg comparing with Metformin reduced 18% of AUC0-2h at the dose of 300 mg/kg.

Treatment of murine lupus with PD-LIg.

The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells has been proven to turn off autoreactive T cells and induce peripheral tolerance. In this study, fusion proteins linking the extracellular domains of murine PD-1, PD-L1 and PD-L2 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody were generated and characterized. Onset of proteinuria was delayed with mice treated with PD-LIg fusion proteins, while serum concentrations of anti-dsDNA and anti-histone antibodies were reduced by the treatment of PD-LIg without decreasing total IgG with significantly improved survival. Importantly, PD-L1Ig treatment was the most efficacious in delaying the onset of proteinuria, blocking auto-antibody production, and prolonging life time, including a delayed treatment until disease progression. These findings indicate that human PD-L1Ig fusion proteins may play an important role in conquering humans' autoimmune diseases.

Does ventilator-associated event surveillance detect ventilator-associated pneumonia in intensive care units? A systematic review and meta-analysis.

BACKGROUND: Ventilator-associated event (VAE) is a new surveillance paradigm for monitoring complications in mechanically ventilated patients in intensive care units (ICUs). The National Healthcare Safety Network replaced traditional ventilator-associated pneumonia (VAP) surveillance with VAE surveillance in 2013. The objective of this study was to assess the consistency between VAE surveillance and traditional VAP surveillance. METHODS: We systematically searched electronic reference databases for articles describing VAE and VAP in ICUs. Pooled VAE prevalence, pooled estimates (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) of VAE for the detection of VAP, and pooled estimates (weighted mean difference (WMD) and odds ratio ([OR)) of risk factors for VAE compared to VAP were calculated. RESULTS: From 2191 screened titles, 18 articles met our inclusion criteria, representing 61,489 patients receiving mechanical ventilation at ICUs in eight countries. The pooled prevalence rates of ventilator-associated conditions (VAC), infection-related VAC (IVAC), possible VAP, probable VAP, and traditional VAP were 13.8 %, 6.4 %, 1.1 %, 0.9 %, and 11.9 %, respectively. Pooled sensitivity and PPV of each VAE type for VAP detection did not exceed 50 %, while pooled specificity and NPV exceeded 80 %. Compared with VAP, pooled ORs of in-hospital death were 1.49 for VAC and 1.76 for IVAC; pooled WMDs of hospital length of stay were -4.27 days for VAC and -5.86 days for IVAC; and pooled WMDs of ventilation duration were -2.79 days for VAC and -2.89 days for IVAC. CONCLUSIONS: VAE surveillance missed many cases of VAP, and the population characteristics identified by the two surveillance paradigms differed. VAE surveillance does not accurately detect cases of traditional VAP in ICUs.

Profiles of responses of immunological factors to different subtypes of Kawasaki disease.

BACKGROUND: The responses of immunological factors to different subtypes of Kawasaki disease (KD) remain poorly understood. METHODS: We recruited 388 patients with KD, 160 patients with infectious febrile disease and 85 normal children who served as control subjects. Both the levels and percentages of T lymphocyte subsets, natural killer cells (NK cells) and B cells were analyzed via flow cytometry. The levels of serum IgG, IgM, IgA and C3, C4 were assessed via velocity scatter turbidimetry. RESULTS: The most significant differences noted between the patients with infectious febrile disease and the normal children were the elevated levels of B cells, C3 and the ratio of CD4/CD8, and the decreased levels of CD8+ T cells and NK cells, as well as the moderate increase in the absolute value of the CD3+ cells. The decreased T cell levels and the elevated B cell levels were helpful in distinguishing typical KD from atypical KD; the elevated T cell levels, the elevated NK cell and B cell levels and the decreased B cell levels were helpful in predicting the effectiveness of IVIG; low C3 and C4 levels were linked with prodromal infections. CONCLUSIONS: Lymphocytes subsets and complement markers may be useful in differentiating among the different subtypes of KD and in helping clinicians understand the pathophysiology of KD.

Impact of a bundle on prevention and control of healthcare associated infections in intensive care unit.

Inpatients in the intensive care unit (ICU) are at high risk for healthcare-associated infections (HAIs). In the current study, a bundle of interventions and measures for preventing and controlling HAIs were developed and implemented in the ICU by trained personnel, and the impact of the bundle was evaluated. The incidence of HAIs, the adjusted daily incidence of HAIs and the incidence of three types of catheter-related infections before and after the bundle implementation were compared. The execution rate of the bundle for preventing and controlling ventilator-associated pneumonia (VAP) was increased from 82.06% in 2012 to 96.88% in 2013. The execution rate was increased from 83.03% in 2012 to 91.33% in 2013 for central line-associated bloodstream infection (CLABSI), from 87.00% to 94.40% for catheter-associated urinary tract infection (CAUTI), and from 82.05% to 98.55% for multidrug-resistant organisms (MDROs), respectively. In total, 136 cases (10.37%) in 2012 and 113 cases (7.72%) in 2013 involved HAIs, respectively. Patients suffered from infection of the lower respiratory tract, the most common site of HAIs, in 134 cases (79.29%) in 2012 and 107 cases (74.30%) in 2013 respectively. The incidence of VAP was 32.72‰ and 24.60‰, the number of strains of pathogens isolated was 198 and 173, and the number of MDROs detected in the ICU was 91 and 74 in 2012 and 2013, respectively. The percentage of MDROs among the pathogens causing HAIs was decreased in each quarter of 2013 as compared with the corresponding percentage in 2012. In 2013, the execution rate of the bundle for preventing and controlling HAIs was increased, whereas the incidence of HAIs and VAP decreased as compared with that in 2012.

The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature.

CD147 or EMMPRIN is a member of the immunoglobulin superfamily in humans. It is widely expressed in human tumors and plays a central role in the progression of many cancers by stimulating the secretion of matrix metalloproteinases (MMPs) and cytokines. CD147 regulates cell proliferation, apoptosis, and tumor cell migration, metastasis and differentiation, especially under hypoxic conditions. CD147 is also important to many organ systems. This review will provide a detailed overview of the discovery, characterization, molecular structure, diverse biological functions and regulatory mechanisms of CD147 in human physiological and pathological processes. In particular, recent studies have demonstrated the potential application of CD147 not only as a phenotypic marker of activated regulatory T cells but also as a potential diagnostic marker for early-stage disease. Moreover, CD147 is recognized as an effective therapeutic target for hepatocellular carcinoma (HCC) and other cancers, and exciting clinical progress has been made in HCC treatment using CD147-directed monoclonal antibodies.

Comparing the Effects of Two Culture Methods to Determine the Total Heterotrophic Bacterial Colony Count in Hospital Purified Water.

BACKGROUND: Accurately detecting the quantity of microorganisms in hospital purified water is of significant importance for early identification of microbial contamination and reducing the occurrence of water-borne hospital infections. The choice of detection method is a prerequisite for ensuring accurate results. Traditional Plate Count Agar (PCA) belongs to a high-nutrient medium, and there may be limitations in terms of accuracy or sensitivity in detecting microorganisms in hospital purified water. On the other hand, Reasoner's 2A agar (R2A) has characteristics, such as low-nutrient levels, low cultivation temperature, and extended incubation time, providing advantages in promoting the growth of aquatic microorganisms. This study, through comparing the differences in total colony counts between two detection methods, aims to select the method more suitable for the growth of aquatic microorganisms, offering new practical insights for accurately detecting the total count of heterotrophic bacteria in hospital purified water. METHODS: The most commonly used plate count agar (PCA) method, and the R2A agar culture were adopted to detect microorganisms and determine the total number of bacterial colonies in the water for oral diagnosis and treatment water and terminal rinse water for endoscopes in medical institutions. The two water samples were inoculated by pour plate and membrane filtration methods, respectively. Using statistical methods including Spearman and Pearson correlation, Wilcoxon signed-rank sum test, paired-Chi-square test, and linear regression, we analyze the differences and associations in the bacterial counts cultivated through two different methods. RESULTS: In 142 specimens of the water, the median and interquartile range of the heterotrophic bacterial colony number under the R2A culture method and under the PCA culture method were 200 (Q1-Q3: 25-18,000) and 6 (Q1-Q3: 0-3700). The total number of heterotrophic bacteria colonies cultured in R2A medium for 7 days was more than that cultured in PCA medium for 2 days (P < 0.05). The linear regression results showed a relatively strong linear correlation between the number of colonies cultured by the R2A method and that cultured by the PCA method (R2 = 0.7264). The number of bacterial species detected on R2A agar medium is greater than that on PCA agar medium. CONCLUSION: The R2A culture method can better reflect the actual number of heterotrophic bacterial colonies in hospital purified water. After logarithmic transformation, the number of colonies cultured by the two methods showed a linear correlation.

Functional metabolomics reveals arsenic-induced inhibition of linoleic acid metabolism in mice kidney in drinking water.

Arsenic (As) is a heavy metal known for its detrimental effects on the kidneys, but the precise mechanisms underlying its toxicity remain unclear. In this study, we employed an integrated approach combining traditional toxicology methods with functional metabolomics to explore the nephrotoxicity induced by As in mice. Our findings demonstrated that after 28 days of exposure to sodium arsenite, blood urea nitrogen, serum creatinine levels were significantly increased, and pathological examination of the kidneys revealed dilation of renal tubules and glomerular injury. Additionally, uric acid, total cholesterol, and low-density lipoprotein cholesterol levels were significant increased while triglyceride level was decreased, resulting in renal insufficiency and lipid disorders. Subsequently, the kidney metabolomics analysis revealed that As exposure disrupted 24 differential metabolites, including 14 up-regulated and 10 down-regulated differential metabolites. Ten metabolic pathways including linoleic acid and glycerophospholipid metabolism were significantly enriched. Then, 80 metabolic targets and 168 predicted targets were identified using metabolite network pharmacology analysis. Of particular importance, potential toxicity targets, such as glycine amidinotransferase, mitochondrial (GATM), and nitric oxide synthase, and endothelial (NOS3), were prioritized through the "metabolite-target-pathway" network. Receiver operating characteristics curve and molecular docking analyses suggested that 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, linoleic acid, and L-hydroxyarginine might be functional metabolites associated with GATM and NOS3. Moreover, targeted verification result showed that the level of linoleic acid in As group was 0.4951 µg/mL, which was significantly decreased compared with the control group. And in vivo and in vitro protein expression experiments confirmed that As exposure inhibited the expression of GATM and NOS3. In conclusion, these results suggest that As-induced renal injury may be associated with the inhibition of linoleic acid metabolism through the down-regulation of GATM and NOS3, resulting in decreased levels of linoleic acid, 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, and L-hydroxyarginine metabolites.

A novel approach combining network pharmacology and experimental validation to study the protective effect of ginsenoside Rb1 against cantharidin-induced hepatotoxicity in mice.

Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targets were the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD.

Curcumin alleviates atrazine-induced cardiotoxicity by inhibiting endoplasmic reticulum stress-mediated apoptosis in mice through ATF6/Chop/Bcl-2 signaling pathway.

Atrazine (ATR), a water-soluble herbicide commonly used to control broad-leaf and monocotyledonous weeds, presents a significant risk to environmental soil and water quality. Exposure to ATR adversely affects human and animal health, frequently resulting in cardiac impairment. Curcumin (Cur), an acidic polyphenol derivative from plants acclaimed for its pronounced anti-inflammatory and antioxidant properties, has garnered interest as a potential therapeutic agent. However, whether it has the potential to ameliorate ATR-induced cardiac toxicity via modulation of endoplasmic reticulum stress (ERS) and apoptosis pathways in mice remains unclear. Our results showed that Cur supplementation attenuates ATR-induced cardiotoxicity, evidenced by decrease in creatine kinase and lactate dehydrogenase, key biochemical markers of myocardial injury, which have a more significant protecting effect in high-dose ATR induced injury. Histopathological and electron microscopy examinations further solidified these findings, demonstrating an amelioration in organellar damage, particularly in endoplasmic reticulum swelling and subsequent mitochondrial impairment. Additionally, ATR exposure augments ERS and triggers apoptotic pathways, as indicated by the upregulation of ERS-related gene expression (ATF6, CHOP, IRE1, GRP78) and pro-apoptotic markers (BAX, BAK1, Caspase3, Caspase. Intriguingly, Cur counteracts this detrimental response, significantly reducing ERS and pro-apoptotic signals at both transcriptional and translational levels. Collectively, our findings illuminate Cur's cardioprotective effect against ATR-induced injury, primarily through its anti-ERS and anti-apoptotic activities, underscoring Cur's potential as a therapeutic for ATR-induced cardiotoxicity.

Piperine improves levodopa availability in the 6-OHDA-lesioned rat model of Parkinson's disease by suppressing gut bacterial tyrosine decarboxylase.

AIM: Tyrosine decarboxylase (TDC) presented in the gut-associated strain Enterococcus faecalis can convert levodopa (L-dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L-dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria-mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L-dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L-dopa on Parkinson's disease (PD). METHODS: Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis. Then, the inhibitory effects of PIP on L-dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L-dopa and PIP on 6-hydroxydopamine (6-OHDA)-lesioned rats and tested the regulations of L-dopa bioavailability and brain DA level by pharmacokinetics study and MALDI-MS imaging. Finally, we evaluated the microbiota-dependent improvement effect of PIP on L-dopa availability using pseudo-germ-free and E. faecalis-transplanted rats. RESULTS: We found that PIP combined with L-dopa could better ameliorate the move disorders of 6-OHDA-lesioned rats by remarkably improving L-dopa availability and brain DA level than L-dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L-dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6-OHDA-lesioned rats. CONCLUSION: Oral administration of L-dopa combined with PIP can improve L-dopa availability and brain DA level in 6-OHDA-lesioned rats by suppressing intestinal bacterial TDC.