Attenuating Renal Interstitial Fibrosis by Shenqi Pill via Reducing Inflammation Response Regulated by NF-κB Pathway In Vitro and In Vivo.

INTRODUCTION: One of the most significant clinical features of chronic  kidney disease is renal interstitial fibrosis (RIF). This study aimed  to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral  ureteral obstruction (UUO) surgery on rat or stimulating human  kidney-2 (HK-2) cell with transforming growth factor ß1 (TGFß1).  After modeling, the rats in the SQP low dose group (SQP-L), SQP  middle dose group (SQP-M) and SQP high dose group (SQP-H)  were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the  TGFß1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing  serum. In in vivo assays, serum creatinine (SCr) and blood urea  nitrogen (BUN) content were measured, kidney histopathology  was evaluated., and α-smooth muscle actin (α-SMA) expression  was detected by immunohistochemistry. Interleukin-1ß (IL-1ß),  interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content,  inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were  assessed. Meanwhile, cell viability, inflammatory cytokines content,  α-SMA expression, IKBα and P65 phosphorylation were detected  in vitro experiment.  Results. SQP exhibited reno-protective effect by decreasing SCr  and BUN content, improving renal interstitial damage, blunting  fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after  the treatment with SQP-containing serum, viability and α-SMA  expression were remarkably decreased in TGFß1-stimulated HK-2  cell. Furthermore, SQP markedly down-regulated IL-1ß, IL-6, and  TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro.  Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa  B (NF-κB) pathway related inflammatory response, which indicates  that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.

Shen Qi Wan-Containing Serum Alleviates Renal Interstitial Fibrosis via Restraining Notch1-Mediated Epithelial-Mesenchymal Transition.

Objective: Shen Qi Wan (SQW) is the most classic prescription for the clinical therapy of chronic kidney disease in China. Nevertheless, the function of SQW in renal interstitial fibrosis (RIF) has not been clearly clarified. Our purpose was to explore the protective function of SQW on RIF. Methods: After intervention with SQW-containing serum alone at increasing concentrations (2.5, 5, and 10%) or in combination with siNotch1, the transforming growth factor-beta (TGF-ß)-induced HK-2 cell viability, extracellular matrix (ECM)-, epithelial-mesenchymal transition (EMT), and Notch1 pathway-associated protein expressions were assessed by cell counting kit-8, qRT-PCR, western blot, and immunofluorescence assays. Results: SQW-containing serum intensified the viability of TGF-ß-mediated HK-2 cells. Besides, it augmented the collagen II and E-cadherin levels, and weakened the fibronectin, α-SMA, vimentin, N-cadherin, and collagen I levels in HK-2 cells triggered by TGF-ß. Moreover, it is found that TGF-ß led to the upregulation of Notch1, Jag1, HEY1, HES1, and TGF-ß in HK-2 cells, which was partially offset by SQW-containing serum. Furthermore, cotreatment of SQW-containing serum and Notch1 knockdown further apparently alleviated the Notch1, vimentin, N-cadherin, collagen I, and fibronectin levels in HK-2 cells induced by TGF-ß. Conclusion: Collectively, these findings elucidated that SQW-containing serum attenuated RIF via restraining EMT through the repression of the Notch1 pathway.

A cross-sectional study on the mental health of patients with COVID-19 1 year after discharge in Huanggang, China.

OBJECTIVE: This study is aimed to investigate the mental health status of COVID-19 survivors 1 year after discharge from hospital and reveal the related risk factors. METHODS: From April 11 to May 11, 2021, 566 COVID-19 survivors in Huanggang city were recruited through their primary doctors. A total of 535 participants (94.5%) admitted to participate in the survey and completed the questionnaires. Five scales were applied including 7-Items Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, Impact of Event Scale-Revised, Pittsburgh Sleep Quality Index, and Fatigue Scale-14. The chi-square and the Fisher's exact test were used to evaluate the classification data, multivariate logistic regression was used to explore the related factors of sleep quality, fatigue, anxiety, depression, and post-traumatic stress disorder (PTSD). RESULTS: One year after being discharged, of the 535 COVID-19 survivors, 252 (47.1%) had poor sleep quality; 157 (29.3%) had the symptoms of fatigue; 84 (15.7%),112 (20.9%), and 130 (24.3%) suffered from symptoms of anxiety, depression, and PTSD, respectively. The logistic regression analysis showed that history of chronic disease was risk factor for poor sleep quality (OR 2.501; 95% CI, 1.618-3.866), fatigue (OR 3.284; 95% CI 2.143-5.033), PTSD (OR 2.323; 95% CI 1.431-3.773) and depression (OR 1.950; 95% CI 1.106-3.436) in COVID-19 survivors. Smoking contributed to the poor sleep quality (OR 2.005; 95% CI 1.044-3.850), anxiety (OR 4.491; 95% CI 2.276-8.861) and depression (OR 5.459; 95% CI 2.651-11.239) in survivors. Drinking influenced fatigue (OR 2.783; 95% CI 1.331-5.819) and PTSD (OR 4.419; 95% CI 1.990-9.814) in survivors. Compared with college-educated survivors, survivors with high school education were at higher risk for poor sleep quality (OR 1.828; 95% CI 1.050-3.181) and PTSD (OR 2.521; 95% CI 1.316-4.830), and survivors with junior high school education were at higher risk for PTSD (OR 2.078; 95% CI 1.039-4.155). Compared with overweight survivors (BMI ≥ 23.0), survivors with normal BMI (18.5-22.9) (OR 0.600; 95% CI 0.405-0.889) were at lower risk for fatigue. While being housewife (OR 0.390; 95% CI 0.189-0.803) was protective factor for fatigue and having more family members was protective factor for PTSD (OR 0.404 95% CI 0.250-0.653) in survivors. CONCLUSIONS: One year after infection, poor sleep quality, fatigue, anxiety, depression, and PTSD, still existed in a relatively high proportion of COVID-19 survivors. Chronic disease history was an independent risk factor for poor sleep quality, fatigue, depression, and PTSD. Participants with low education levels were more likely to have mental problems than the others. We should focus on the long-term psychological impact of COVID-19 on survivors, and the government should apply appropriate mental health services to offer psychiatric support.

Shen Qi Wan Ameliorates Learning and Memory Impairment Induced by STZ in AD Rats through PI3K/AKT Pathway.

Alzheimer's disease is the most common form of neurodegenerative disease, and increasing evidence shows that insulin signaling has crucial roles in AD initiation and progression. In this study, we explored the effect and underlying mechanism of SQW, a representative formula for tonifying the kidney and promoting yang, on improving the cognitive function in a streptozotocin-induced model of AD rats. We investigated memory impairment in the AD rats by using the Morris water test. HE and Nissl staining were employed to observe the histomorphological changes in the hippocampal. Expression levels of NeuN and proteins related to Tau and apoptosis were measured using immunohistochemistry and Western blotting, respectively. Additionally, we performed RNA sequencing, and the selected hub genes were then validated by qRT-PCR. Furthermore, the protein expression levels of PI3K/AKT pathway-related proteins were detected by Western blot. We found that SQW treatment significantly alleviated learning and memory impairment, pathological damage, and apoptosis in rats, as evidenced by an increased level of NeuN and Bcl-2, and decreased phosphorylation of Tau, Bax, and Caspase-3 protein expression. SQW treatment reversed the expression of insulin resistance-related genes (Nr4a1, Lpar1, Bdnf, Atf2, and Ppp2r2b) and reduced the inhibition of the PI3K/AKT pathway. Our results demonstrate that SQW could contribute to neuroprotection against learning and memory impairment in rats induced by STZ through activation of the PI3K/AKT pathway.

Circ_0007142 downregulates miR-874-3p-mediated GDPD5 on colorectal cancer cells.

BACKGROUND: Ferroptosis is an iron-dependent and oxidative cell death form. Recent studies suggested that circular RNAs (circRNAs) regulated ferroptosis in tumour cells. Circ_0007142 was identified as a carcinogenic molecule in colorectal cancer (CRC), but its function on ferroptosis in CRC remains unknown. METHODS: Circ_0007142, microRNA-874-3p (miR-874-3p) and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) levels were assayed using the quantitative real-time polymerase chain reaction (qRT-PCR). Cell survival and proliferation were measured by Cell Counting Kit-8 (CCK-8) assay. Protein detection was performed by Western blot. Cell apoptosis was analysed by flow cytometry. Ferroptosis was assessed by iron accumulation and oxidative stress. Target binding was evaluated by dual-luciferase reporter assay. In vivo research was conducted by tumour xenograft in mice. RESULTS: Circ_0007142 was overexpressed in CRC. After expression inhibition of circ_0007142, proliferation was reduced, while apoptosis and ferroptosis were facilitated in CRC cells. Mechanically, circ_0007142 was found as a miR-874-3p sponge and miR-874-3p inhibitor eliminated the regulation of si-circ_0007142 in CRC cells. MiR-874-3p targeted GDPD5 and upregulation of GDPD5 reversed the miR-874-3p-triggered tumour inhibition and ferroptosis promotion in CRC cells. Moreover, GDPD5 was regulated by the circ_0007142/miR-874-3p axis. Circ_0007142 also affected CRC tumorigenesis in vivo through the regulation of miR-874-3p and GDPD5. CONCLUSION: All these findings proved that circ_0007142/miR-874-3p/GDPD5 axis regulated tumorigenesis and ferroptosis of CRC cells. Circ_0007142 might be an available marker for ferroptosis in CRC therapy.

The Protective Effect of Shen Qi Wan on Adenine-Induced Podocyte Injury.

Podocytes are a special type of differentiated epithelial cells that maintain the glomerular filtration barrier in the kidney. Injury or damages in podocytes can cause kidney-related disorders, like CKD. The injury or dysfunction of podocytes can occur by different metabolic disorders. Due to the severity and complexity of podocyte injuries, this state is considered as a serious health issue worldwide. Here, we examined and addressed the efficacy of an alternative Chinese medicine, Shen Qi Wan (SQW), on podocyte-related kidney injury. We evaluated the role and mechanism of action of SQW in podocyte injury. We observed that SQW significantly reduced 24-hour urinary protein and blood urea nitrogen levels and alleviated the pathological damage caused by adenine. Moreover, SQW significantly decreased the expression of nephrin and increased the expression of WT1 and AQP1 in the kidney of mice treated with adenine. We observed that SQW did not effectively reduce the high level of proteinuria in AQP1-/- mice indicating the prominent role of AQP1 in the SQW-ameliorating pathway. Transmission electron microscopy (TEM) images indicated the food processes effacement in AQP1-/- mice were not lessened by SQW. In conclusion, podocyte injury could alter the pathological nature of the kidney, and SQW administration relieves the nature of pathogenesis by activating AQP1.

The Influence of Information Intervention Cognition on College Students' Energy-Saving Behavior Intentions.

Based on the theory of planned behavior, this research examines the influence of different types of information on the behavioral intentions of college students in the context of perceived behavioral control (perceived self-efficacy and perceptual control) as mediating variables. The results showed that: (1) Different types of information intervention factors have different effects on perceptual self-efficacy and perceptual control; the influence degree of economic cost has the strongest effect, followed by group pressure, while the influence degree of publicity and education has the weakest effect. However, policy intervention has no statistically significant effect on both of them (perceived self-efficacy and perceptual control). (2) Two variables, perceived self-efficacy and perceptual control, serve as mediators between information intervention factors and energy-saving behavior intention. (3) Individual characteristic factors have significant moderating effects on each path in the model of information intervention-perceived behavior control-intention. Finally, suggestions are made on how to encourage college students to more effectively save energy.

Exploiting Implicit Influence From Information Propagation for Social Recommendation.

Social recommender systems have attracted a lot of attention from academia and industry. On social media, users' ratings and reviews can be observed by all users, and have implicit influence on their future ratings. When these users make subsequent decisions about an item, they may be affected by existing ratings on the item. Thus, implicit influence propagates among the users who rated the same items, and it has significant impact on users' ratings. However, implicit influence propagation and its effect on recommendation rarely have been studied. In this article, we propose an information propagation-based social recommendation method (SoInp) and model the implicit user influence from the perspective of information propagation. The implicit influence is inferred from ratings on the same items. We investigate the concrete effect of implicit user influence in the propagation process and introduce it into recommender systems. Furthermore, we incorporate the implicit user influence and explicit trust information in the matrix factorization framework. To demonstrate the performance, we conduct comprehensive experiments on real-world datasets to compare the proposed method with the state-of-the-art models. The results indicate that SoInp makes notable improvements in rating prediction.

Correlation between the rs7101 and rs1063169 polymorphisms in the FOS noncoding region and susceptibility to and prognosis of colorectal cancer.

BACKGROUND: The FOS gene is located on human chromosome 14q21-31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. METHODS: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan-Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. RESULTS: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131-1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111-1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues (P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS (P < .05). CONCLUSION: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.

Flavanones from Sedum sarmentosum Bunge Alleviate CCl4-Induced Liver Fibrosis in Rats by Targeting TGF-ß1/TßR/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition.

OBJECTIVE: The aim of the study is to evaluate the therapeutic effects of flavanones from Sedum sarmentosum Bunge (FSSB) on CCl4-induced liver fibrosis in rats and the underlying mechanisms of action. METHODS: An experimental model of liver fibrosis was established by subcutaneous injection of rats with CCl4 (40% v/v, 3 ml/kg) twice per week for six weeks. FSSB (100, 200, and 400 mg/kg) was intragastrically administered once per day consecutively for five weeks. RESULTS: Our results showed that FSSB significantly attenuated CCl4-induced liver fibrosis as evidenced by reducing the elevated levels of serum biochemical indexes and improving the histological changes, including decreasing the elevation in serum alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), and laminin (LN) level, reducing infiltration of inflammatory cells and collagen fibers in liver tissue. In addition, compared to the model group, FSSB markedly downregulated the protein and mRNA expression of TGF-ß1, TGF-ß1 receptors I and II (TßRI and TßRII), Smad2, Smad3, and Vimentin in liver tissue, at the mean time upregulating the expression of Smad7 and E-cadherin. CONCLUSIONS: The results suggest that FSSB alleviated CCl4-induced liver fibrosis probably through inhibition of TGF-ß/TßR/Smad pathway in turn inhibiting epithelial mesenchymal transition.

[Effect of Zhenwu Tang on regulating of "AVP-V2R-AQP2" pathway in NRK-52E cells].

This study was aimed to investigate the effect and mechanism of Zhenwu Tang on AVP-V2R-AQP2 pathway in NRK-52E cells in vitro. Forty eight male SD rats were randomly divided into eight groups with 6 animals in each group. Distilled water or 22.68 g·kg⁻¹·d⁻¹ Zhenwu Tang(calculated by raw drug dosage meter) was given by gavage. Blood samples were collected by cardiac puncture， and the medicated serum was centrifuged from the blood by 3 000 r·min⁻¹. NRK-52E cells were treated with different medicated serum or dDAVP. The condition of cell proliferation was detected by RTCA. The distribution of V2R and AQP2 in cells were detected by immunofluorescence. The expression of V2R， PKA and AQP2 were detected by Western blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the level of AQP2 mRNA(P<0.01) and protein expression of V2R， PKA and AQP2(P<0.05， P<0.01， P<0.05) of Z7d group which was treated with Zhenwu Tang medicated serum for 24 h were significantly higher than that of normal rat serum group. And the expression level of V2R， p-AQP2 and AQP2(P<0.01， P<0.05， P<0.01) of Z7d+dDAVP group were significantly increased comparing to normal rat serum group. The results indicate that the applying of Zhenwu Tang medicated serum could increase the expression level of V2R， PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in NRK-52E， and there is synergistic effect between Zhenwu Tang medicated serum and dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which Zhenwu Tang regulate balance of water transportation.

GABA and 5-HT Systems Are Involved in the Anxiolytic Effect of Gan-Mai-Da-Zao Decoction.

The Gan-Mai-Da-Zao (GMDZ) decoction is one of the most famous Chinese medicine prescriptions to treat emotional diseases in China. Here we examined the anxiolytic-like effects of the GMDZ decoction in mice. The mice were orally administered with GMDZ decoction (1, 2, and 4 g/kg, respectively) for 7 days, diazepam (2 mg/kg, p.o.) and buspirone (5 mg/kg, p.o.) were used as positive controls. Then, elevated plus maze (EPM) test, light/dark box (LDB) test, and marble burying (MB) test, open field (OF) test and rota-rod test were performed. We found that GMDZ treatment (2 and 4 g/kg) significantly increased the percentage of open arm entries and time spent on the open arms in EPM as compared to the control. GMDZ treatment also significantly increased the time spent in the light box and the number of light box entries in LDB and reduced the number of marbles buried in MB. Similarly to those observed with diazepam and buspirone. In contrast, GMDZ did not affect the locomotor activity in the OF and motor coordination in the rota-rod test. Furthermore, the anxiolytic-like effects induced by GMDZ were inhibited by the γ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil and 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635. These results showed that GMDZ possesses anxiolytic-like effects in animal models, and its mechanism of action might be modulated by 5-HT1A and GABAA receptors.

Shenqiwan Ameliorates Renal Fibrosis in Rats by Inhibiting TGF-ß1/Smads Signaling Pathway.

Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-ß1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1.5 g/kg, 3 g/kg, and 6 g/kg. Control group and model group were given the same volume of saline. Meanwhile, the positive control group was treated with Enalapril (4 mg/kg). Animals were sacrificed on 21st day after administration. The results showed that SQW could significantly relieve renal pathological damage caused by adenine, increase gene and protein expression of E-cadherin, and decrease the expression of Vimentin in kidney samples. In addition, SQW efficiently inhibited the mRNA and protein expression of p-Smad2/3 by upregulating Smad7. These results suggest that SQW could slow down the progression of renal fibrosis, possibly by inhibiting TGF-ß1/Smads signaling pathway.

Neuroprotective Effects and Mechanism of ß-Asarone against Aß1-42-Induced Injury in Astrocytes.

Emerging evidence suggests that activated astrocytes play important roles in AD, and ß-asarone, a major component of Acorus tatarinowii Schott, was shown to be a potential therapeutic candidate for AD. While our previous study found that ß-asarone could improve the cognitive function of rats hippocampally injected with Aß, the effects of ß-asarone on astrocytes remain unclear, and this study aimed to investigate these effects. A rat model of Aß1-42 (10 µg) was established, and the rats were intragastrically treated with ß-asarone at doses of 10, 20, and 30 mg/kg or donepezil at a dose of 0.75 mg/kg. The sham and model groups were intragastrically injected with an equal volume of saline. Animals were sacrificed on the 28th day after administration of the drugs. In addition, a cellular model of Aß1-42 (1.1 µM, 6 h) was established, and cells were treated with ß-asarone at doses of 0, 2.06, 6.17, 18.5, 55.6, and 166.7 µg/mL. ß-Asarone improved cognitive impairment, alleviated Aß deposition and hippocampal damage, and inhibited GFAP, AQP4, IL-1ß, and TNF-α expression. These results suggested that ß-asarone could alleviate the symptoms of AD by protecting astrocytes, possibly by inhibiting TNF-α and IL-1ß secretion and then downregulating AQP4 expression.

Toward Bayesian chemometrics--a tutorial on some recent advances.

Chemometrics is increasingly being perceived as a maturing science. While this perception seems to be true with regards to the traditional methods and applications of chemometrics, this article argues that advances in instrumentation, computation, and statistical theory may combine to drive a resurgence in chemometrics research. Previous surges in chemometrics research activity were driven by the development of new ways of making better use of available information. Bayesian statistics can further enhance the ability to use domain specific information to obtain more accurate and useful models, and presents many research opportunities as well as challenges. Although Bayesian statistics is not new, recent advances via sampling-based Monte Carlo methods make these methods practical for large scale applications without making the common assumptions of Gaussian noise and uniform prior distributions, made by most chemometric methods. This article provides an overview of traditional chemometric methods from a Bayesian view and a tutorial of some recently developed techniques in Bayesian chemometrics, such as Bayesian PCA and Bayesian latent variable regression. New challenges and opportunities for future work are also identified.