Defining the threshold: triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio's non-linear impact on tubular atrophy in primary membranous nephropathy.

Background: Hyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients. Methods: We conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People's Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results. Results: Of the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA. Conclusion: Our study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies.

Correlation Analysis between Intrarenal Small Artery Intimal Thickening and Clinicopathological Features and Prognosis in Primary Membranous Nephropathy Patients.

BACKGROUND: Primary membranous nephropathy (PMN) is the most common pathological type of nephrotic syndrome in adults. Intrarenal small artery intimal thickening can be observed in most renal biopsies. The purpose of this study was to investigate the association between intrarenal small artery intimal thickening and clinicopathological features and prognosis in PMN patients. METHODS: Data were continuously collected from patients who were diagnosed with PMN in Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University) from 2008 to 2021 for a retrospective cohort study. Regression analysis and survival analysis were used to analyze the relationship between intrarenal small artery intimal thickening and renal prognosis in PMN patients. RESULTS: 300 PMN patients were enrolled in this study, including 165 patients (55%) with intrarenal small artery intimal thickening. Patients with intimal thickening were older, with higher BMI, systolic blood pressure and diastolic blood pressure, serum uric acid, a higher proportion of hypertension, acute kidney injury, nephrotic syndrome, more urine protein, and lower eGFR. Multivariate Cox regression analysis showed that after adjusting for age, gender, hypertension, BMI, urine protein, eGFR, and the use of ACEI/ARB and hormone immunosuppressants, intimal thickening was a risk factor for renal prognosis in PMN patients (HR = 3.68, 95% CI 1.36-9.96, p < 0.05). Kaplan-Meier survival curve analysis showed that the incidence of reaching the renal composite outcome was higher in the intimal thickening group (p < 0.05). CONCLUSION: The prognosis of PMN patients with intrarenal small artery intimal thickening is worse, so early intervention is very important for these patients.

Baicalin/ambroxol hydrochloride combined dry powder inhalation formulation targeting lung delivery for treatment of idiopathic pulmonary fibrosis: Fabrication, characterization, pharmacokinetics, and pharmacodynamics.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal lung disease caused by multiple factors. Currently, safe, and effective drugs for the treatment of IPF have been extremely scarce. Baicalin (BA) is used to treat pulmonary fibrosis, IPF, chronic obstructive pulmonary disease, and other lung diseases. Ambroxol hydrochloride (AH), a respiratory tract lubricant and expectorant, is often used to treat chronic respiratory diseases, such as bronchial asthma, emphysema, tuberculosis, and cough. The combination of BA and AH can relieve cough and phlegm, improve lung function, and potentially treat IPF and its symptoms. However, given the extremely low solubility of BA, its bioavailability for oral absorptions is also low. AH, on the other hand, has been associated with certain side effects, such as gastrointestinal tract and acute allergic reactions, which limit its applicability. Therefore, an efficient drug delivery system is urgently needed to address the mentioned problems. This study combined BA and AH as model drugs with L-leucine (L-leu) as the excipient to prepare BA/AH dry powder inhalations (BA/AH DPIs) using the co-spray drying method. We the performed modern pharmaceutical evaluation, which includes particle size, differential scanning calorimetry analysis, X-ray diffraction, scanning electron microscope, hygroscopicity, in vitro aerodynamic analysis, pharmacokinetics, and pharmacodynamics. Notably, BA/AH DPIs were found to be advantageous over BA and AH in treating IPF and had better efficacy in improving lung function than did the positive drug pirfenidone. The BA/AH DPI is a promising preparation for the treatment of IPF given its lung targeting, rapid efficacy, and high lung bioavailability.

Intraduodenal Delivery of Exosome-Loaded SARS-CoV-2 RBD mRNA Induces a Neutralizing Antibody Response in Mice.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has presented numerous challenges to global health. Vaccines, including lipid-based nanoparticle mRNA, inactivated virus, and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and have been immensely helpful in controlling the pandemic. Here, we present and assess an oral mRNA vaccine based on bovine-milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor-binding domain (RBD) as an immunogen. The results indicate that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptides in 293 cells in vitro and stimulates neutralizing antibodies against RBD in mice. These results indicate that SARS-CoV-2 RBD mRNA vaccine loading with bovine-milk-derived exosomes is an easy, cheap, and novel way to introduce immunity against SARS-CoV-2 in vivo. Additionally, it also can work as a new oral delivery system for mRNA.

Herb-drug interaction of Xingnaojing injection and Edaravone via pharmacokinetics, mixed inhibition of UGTs, and molecular docking.

BACKGROUND: Xingnaojing injection (XNJ) is a famous emergency Traditional Chinese medicine (TCM) derived from the classical Chinese prescription named An-Gong-Niu-Huang Pill. XNJ is often used along with Edaravone injection (EDA) to treat acute ischemic stroke, they have a synergistic effect in improving patients' blood coagulation and neurological function. However, this combination also causes herb-drug interactions (HDIs), raising the risk of adverse reactions. At present, little is known about the pharmacokinetics and potential mechanism of XNJ combined with EDA. PURPOSE: This study investigates the pharmacokinetics and potential mechanism of the HDIs between XNJ and EDA. STUDY DESIGN AND METHODS: The pharmacokinetic interactions between XNJ and EDA were studied by GC-MS in rats, and the inhibition of XNJ and (-)-borneol on UDP-glucuronosyltransferase (UGTs) were assayed by LC-MS/MS in vitro. In vitro-in vivo extrapolation (IVIVE) and molecular docking were performed to reveal the potential for HDIs. RESULTS: The AUC0-∞ of (-)-borneol was increased by 1.25-fold in group EDA+XNJ 10 min later, and the Cmax of edaravone was increased by 1.6-fold in group XNJ+EDA 10 min later (p < 0.05). XNJ and (-)-borneol inhibited UGTs-mediated edaravone metabolism in HLM and RLM with a similar inhibitory intensity, in which both of them have stronger inhibition in RLM. These findings demonstrated that (-)-borneol in XNJ mainly exerted UGTs inhibition, which was consistent with the pharmacokinetic assays. (-)-Borneol moderately inhibited UGT2B7 and UGT1A6 by a mixed inhibition mechanism, with Ki values of 101.393 and 136.217 µM, respectively. Due to the blood concentration of injection was dramatically increased, the HDIs caused by the inhibitory effect of XNJ on UGTs should be highly emphasized. The binding energies of (-)-borneol and edaravone toward UGT2B7 were -6.254 and -6.643 kcal/mol, and the scores towards UGT1A6 were -5.220 and -6.469 kcal/mol, respectively. Moreover, (-)-borneol has similar free energies to many drugs metabolized by UGT2B7 and UGT1A6. CONCLUSIONS: (-)-Borneol modulates the pharmacokinetic behavior of edaravone via mixed inhibition of UGT2B7 and UGT1A6. It provides a theoretical basis for the synergistic effect of XNJ and EDA combinations in clinical practice. When XNJ is used along with UGT2B7 and UGT1A6 substrates, it should be used clinically with caution.

The Flavonoid Components of Scutellaria baicalensis: Biopharmaceutical Properties and their Improvement using Nanoformulation Techniques.

Scutellaria baicalensis georgi, known as "Huangqin" in its dried root form, is a herb widely used in traditional Chinese medicine for "clearing away heat, removing dampness, purging fire and detoxification". Baicalin, baicalein, wogonin, and wogonoside are the main flavonoid compounds found in Scutellaria baicalensis. Scutellaria baicalensis flavonoid components have the potential to prevent and treat a host of diseases. The components of S. baicalensis have limited clinical application due to their low water solubility, poor permeability, and microbial transformation in vivo. Nanopharmaceutical techniques can improve their biopharmaceutical properties, enhance their absorption in vivo, and improve their bioavailability. However, due to the limited number of clinical trials, doubts remain about their toxicity and improvements in human absorption as a result of nanoformulations. This review summarizes the latest and most comprehensive information regarding the absorption, distribution, metabolism, and excretion of the Scutellaria baicalensis components in vivo. We examined the main advantages of nanodrug delivery systems and collected detailed information on the nanosystem delivery of the Scutellaria baicalensis components, including nanosuspensions and various lipid-based nanosystems. Lipid-based systems including liposomes, solid lipid nanoparticles, nanoemulsions, and self-micro emulsifying drug delivery systems are introduced in detail. In addition, we make recommendations for related and future research directions. Future research should further examine the absorption mechanisms and metabolic pathways of nanoformulations of the components of Scutellaria baicalensis in vivo, and accurately track the in vivo behavior of these drug delivery systems to discover the specific reasons for the enhanced bioavailability of nanoformulations of the scutellaria baicalensis components. The development of targeted oral administration of intact nanoparticles of Scutellaria baicalensis components is an exciting prospect.

The anti-tumor and renoprotection study of E-[c(RGDfK)2]/folic acid co-modified nanostructured lipid carrier loaded with doxorubicin hydrochloride/salvianolic acid A.

BACKGROUND: Poor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell surface and their specific ligands provide a basis for targeting tumor cells. However, the differences in the expression levels of these receptors on the tumor cell surface limit the clinical application of anti-tumor preparations modified by a single ligand. Meanwhile, toxicity of chemotherapeutic drugs leads to poor tolerance to anti-tumor therapy. The discovery of natural active products antagonizing these toxic side effects offers an avenue for relieving cancer patients' pain during the treatment process. Since the advent of nanotechnology, interventions, such as loading appropriate drug combinations into nano-sized carriers and multiple tumor-targeting functional modifications on the carrier surface to enhance the anti-tumor effect and reduce toxic and side effects, have been widely used for treating tumors. RESULTS: Nanocarriers containing doxorubicin hydrochloride (DOX) and salvianolic acid A (Sal A) are spherical with a diameter of about 18 nm; the encapsulation efficiency of both DOX and salvianolic acid A is greater than 80%. E-[c(RGDfK)2]/folic acid (FA) co-modification enabled nanostructured lipid carriers (NLC) to efficiently target a variety of tumor cells, including 4T1, MDA-MB-231, MCF-7, and A549 cells in vitro. Compared with other preparations (Sal A solution, NLC-Sal A, DOX solution, DOX injection, Sal A/DOX solution, NLC-DOX, NLC-Sal A/DOX, and E-[c(RGDfK)2]/FA-NLC-Sal A/DOX) in this experiment, the prepared E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had the best anti-tumor effect. Compared with the normal saline group, it had the highest tumor volume inhibition rate (90.72%), the highest tumor weight inhibition rate (83.94%), led to the highest proportion of apoptosis among the tumor cells (61.30%) and the lowest fluorescence intensity of proliferation among the tumor cells (0.0083 ± 0.0011). Moreover, E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had a low level of nephrotoxicity, with a low creatinine (Cre) concentration of 52.58 µmoL/L in the blood of mice, and no abnormalities were seen on pathological examination of the isolated kidneys at the end of the study. Sal A can antagonize the nephrotoxic effect of DOX. Free Sal A reduced the Cre concentration of the free DOX group by 61.64%. In NLC groups, Sal A reduced the Cre concentration of the DOX group by 42.47%. The E-[c(RGDfK)2]/FA modification reduced the side effects of the drug on the kidney, and the Cre concentration was reduced by 46.35% compared with the NLC-Sal A/DOX group. These interventions can potentially improve the tolerance of cancer patients to chemotherapy. CONCLUSION: The E-[c(RGDfK)2]/FA co-modified DOX/Sal A multifunctional nano-drug delivery system has a good therapeutic effect on tumors and low nephrotoxicity and is a promising anti-cancer strategy.

[Prediction of formability of flavonoid extract granules by dry granulation based on design space and RBFNN].

In this paper, a flavonoid extract powder properties-process parameters-granule forming rate prediction model was constructed based on design space and radial basis function neural network(RBFNN) to predict the formability of flavonoid extract gra-nules. Box-Behnken experimental design was employed to explore the mathematical relationships between critical process parameters and quality attributes. The design space of critical process parameters was developed, and the accuracy of the design space was verified by Monte Carlo method(MC). Design Expert 10 was used for Box-Behnken design and mixture design. Scutellariae Radix mixed powder was prepared and its powder properties were measured. The mixed powder was then subjected to dry granulation and the granule forming rate was determined. The correlations between powder properties were analyzed by variance influence factor(VIF), and principal component analysis(PCA) was performed for the factors with strong collinearity. In this way, a prediction model of powder properties-process parameters-granule forming rate was established based on RBFNN, the accuracy of which was evaluated with examples. The results showed that the model had a good predictive effect on the granule forming rate, with the average relative error of 1.04%. The predicted value and the measured value had a high degree of fitting, which indicated that model presented a good prediction ability. The prediction model established in this study can provide reference for the establishment of quality control methods for Chinese medicinal preparations with similar physical properties.

The Nanostructured lipid carrier gel of Oroxylin A reduced UV-induced skin oxidative stress damage.

Oxidative stress damage caused by sun exposure damages the appearance and function of the skin, which is one of the essential inducements of skin aging and even leads to skin cancer. Oroxylin A (OA) is a flavonoid with excellent antioxidant activity and has protective effects against photoaging induced by UV irradiation. However, the strong barrier function of the skin stratum corneum prevents transdermal absorption of the drug, which limits the application of OA in dermal drug delivery. Studies have shown that nanostructured lipid carriers (NLC) can promote not only transdermal absorption of drugs but also increase drug stability and control drug release efficiency, which has broad prospects for clinical applications. In this paper, NLC loaded with OA (OA-NLC) was prepared in order to improve the skin permeability and stability of OA. In vitro studies revealed that OA-NLC had better therapeutic effects than OA solution (OA-Sol) in the cellular model of UVB radiation. OA-Sol and OA-NLC were immobilized in a hydrogel matrix to facilitate application to the dorsal skin of mice. It was found that OA-NLC-gel showed significant antioxidant and anti-apoptotic activity compared to OA-Sol-gel, which was able to protect against skin damage in mice after UV radiation. These results suggest that OA-NLC can improve the deficiencies of OA in skin delivery and show better resistance to UV-induced oxidative damage. The application of OA-NLC to skin delivery systems has good prospects and deserves further development and investigation.

Natural medicine combined with nanobased topical delivery systems: a new strategy to treat psoriasis.

Psoriasis, an autoimmune inflammatory skin disorder, is one of the commonest immune-mediated disease conditions affecting individuals globally. At the moment, the conventional methods applied against psoriasis treatment have various drawbacks involving limited efficacy, skin irritation, immunosuppression, etc. Therefore, it is important for scientists to find a more potent and alternative drug approach towards psoriasis therapeutics. Natural medicine still remains an important source for new drug discovery due to its therapeutical significance in various drug administration routes. However, the traditional formulation of topical therapies for psoriasis is limited in efficacy, which limits the use of natural medicine. Based on the aforementioned limitations, the use of nanocarriers in preparation of these topical herbal products could be tremendously beneficial in enhancing the efficacy of topical medications. Growing pieces of evidence have proposed that the utilization of nanocarriers in transdermal preparation as a prospective technique, with regards to better potency, directs drug absorption to site of action, and minimum toxicity effect respectively. In the course of this review, we emphasized the pathological mechanism of psoriasis, natural medicine formula, active components of natural medicine, and nanopreparations used in the treatment of psoriasis.

In vitro skin retention and drug permeation study of Tongluo-Qutong rubber plaster by UPLC/UV/MS/MS

Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion

Development and evaluation studies of Corylin loaded nanostructured lipid carriers gel for topical treatment of UV-induced skin aging.

We prepared nanostructured lipid carriers (NLC) to promote skin permeation of Corylin so that it can increase its effect on photoaging. Corylin-NLCs were prepared and characterized based on morphology, particle size, zeta potentials, FTIR and DSC. In vitro, we assess the cytotoxicity and lactate dehydrogenase (LDH) of HaCaT cells irradiated by UVB. Expression of antioxidant enzymes was evaluated by commercial kits. The effects of Corylin-NLC on apoptosis were confirmed by flow cytometry and western blotting. In vivo, we use UV irradiated mouse as the oxidative stress model to assess the therapeutic effect of Corylin loaded NLC gel. We identified the Corylin-NLCs can significantly suppress the LDH release, decrease MDA content, increase in CAT, SOD, GSH-Px activity, increase the expression of Bcl-2/Bax protein and reduce the expression of cleaved caspase-3/caspase-3 protein on UVB induced HaCaT cells. The histopathological lesions were significantly improved and observably decreased MDA level, increase in antioxidant enzymes activity in serum of mice by pretreatment of Corylin-NLCs gel. Overall, this study proposes a promising strategy for improving the therapeutic efficacy of photoaging.

Preparation and evaluation of a water-in-oil nanoemulsion drug delivery system loaded with salidroside.

Salidroside (SAL) is a phenolic substance with high solubility and low permeability, which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora, resulting in lower bioavailability. The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL (w/o SAL-N) to explore its suitability in oral drug delivery systems. In this work, SAL-N was successfully prepared by water titration method at Km = 1 to construct the pseudo-ternary phase diagrams. Physical characterization including the average viscosity, pH, refractive index, particle size, PDI, TEM, DSC, the content of SAL, and stability study were performed. It was evaluated for drug release in vitro and pharmacokinetic studies in vivo. The optimized nanoemulsion formulation consisted of Labrafil M 1944CS (63%), Span-80/Tween-80/EtOH (27%) and 200 mg∙mL-1 SAL solution (SAL-SOL) (10%). Low viscosity and suitable pH were expected for the nanoemulsion. The spherical morphology and nanoscale size of SAL-N enhanced the stability of the nanoemulsion system. In vitro drug release showed that SAL-N had a better controlled release property than SAL-SOL at earlier time points. The pharmacokinetic studies exhibited that SAL-N had significantly higher in t1/2 (2.11-fold), AUC0-48 h (1.75-fold) and MRT0-48 h (2.63-fold) than SAL-SOL (P < 0.01). The w/o SAL-N prepared in this work can be effectively delivered via the oral route. It can be seen w/o nanoemulsion is a strategy for the drug with polyphenols to delay the release, enhance oral absorption and reduce metabolic rate.

A mathematical model for quality evaluation of total saponins of Panax japonicas based on hypolipidemic activity.

Objective: The chemical finger printing-based methods for evaluating TCMs quality can report partial of TCMs quality without linking to effective constituents. In this study, a mathematical model was established for the quality evaluation of total saponins of Panax japonicus (TSPJ), a folk medicine in China and Japan for treating diseases, through coupling the dynamic changes of chemical constitutions with corresponding activities. Methods: High-performance liquid chromatography (HPLC) fingerprints were applied to establish the chromatographic database of TSPJ. The associated hypolipidemic activity database was determined by TG assay using HepG2 cell model. Correlation analyses of two databases were performed by partial least squares (PLS) for calculating regression coefficients, and the interval value of YZL value (the ratio of positive and negative peak-to-peak area coefficient) closely related to hypolipidemic activity was refined by the formula of Norminv function to value the quality of TSPJ. Results: In this study, the chromatographic data of 16 common peaks were obtained from 20 batches of TSPJ. After the estimate by this mathematical evaluation model, seven peaks were positively correlated with hypolipidemic activity, and nine peaks were negatively correlated with hypolipidemic activity. When the YZL value was less than 0.7861, the quality of sample was inferior, while YZL value was more than 6.6992, and the quality of samples was superior. The quality of another ten batches of TSPJ was further assessed to verify this method. Conclusion: These results indicated that the established model could be usefully applied to evaluate the quality of TSPJ in the hypolipidemic activity.

Glomerulosclerosis predicts poor renal outcome in patients with idiopathic membranous nephropathy.

OBJECTIVE: This study aimed to investigate the association between the proportion of glomerulosclerosis (focal segmental glomerulosclerosis and/or global glomerulosclerosis) and renal prognosis in patients with idiopathic membranous nephropathy (IMN). METHODS: A retrospective analysis performed from January 2008 to December 2017 in the First Affiliated Hospital of Shenzhen University by renal biopsy confirmed 200 patients with IMN, and their clinical pathology and prognosis were compared. Patients were divided into three groups on the basis of glomerular sclerosis proportion tertiles: low (Tertile1 group, proportion of glomerulosclerosis, 0-0%), middle (Tertile2 group, proportion of glomerulosclerosis, 0-5.5%) and high (Tertile3 group, proportion of glomerulosclerosis, 5.8-72.7%) tertiles. The follow-up endpoints were decreased estimated glomerular filtration rate (eGFR) by 20%, end-stage renal disease, and all-cause mortality. RESULTS: (1) Both, the Tertile1 and Tertile2, groups had significantly lower albumin level and higher 24-h urine protein level than that in the Tertile3 group. Regarding treatment, as the proportion of glomerulosclerosis increases, a more aggressive treatment with glucocorticoids and immunosuppressants should be provided. (2) Correlation analysis showed that the proportion of glomerulosclerosis was positively associated with age (P < 0.05). However, it was negatively associated with eGFR (P < 0.05). (3) Renal tubular atrophy and renal interstitial inflammatory cell infiltration were considered independent correlative factors for glomerulosclerosis. Kaplan-Meier analysis revealed that renal survival rate was significantly lower in patients with a proportion of glomerulosclerosis ≥ 6.45% than in patients with a proportion of glomerulosclerosis < 6.45%. Cox regression analysis revealed that as the proportion of glomerulosclerosis increases, the risk of renal outcomes increases gradually. CONCLUSIONS: Patients in the Tertile3 (higher proportion of glomerulosclerosis) group had more severe renal pathological damage compared to patients in the Tertile1 and Tertile2 groups. Glomerulosclerosis is a risk factor for renal function progression and poor renal prognosis in patients with IMN. As the proportion of glomerulosclerosis increases, the risk of renal endpoint events increases gradually.

History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: the root of Stephania tetrandra S. Moore, known as Fangji in China (Chinese: ), is a traditional Chinese medicine (TCM) with a long history of use. Fangji is a type of medicine used to treat various diseases, including rheumatism, arthralgia, edema and beriberi, unfavorable urination, and eczema. AIM OF THIS REVIEW: There are many newly published reports on the history of uses, phytochemistry, pharmacological activity, quality control and toxicity of Fangji; however, no comprehensive systematic review exists. Therefore, the purpose of this review is to compile the latest and most comprehensive information on Fangji and provide a scientific basis for future research. MATERIALS AND METHODS: A systematic literature search was conducted using multiple electronic databases, including SciFinder, Web of Science, PubMed, Science Direct, ACS Publications, J-stage, SpringerLink, Thieme, Wiley, and CNKI. Information was also collected from journals and Chinese Pharmacopoeia. RESULT: Thus far, there were uses of Fangji against 20 different diseases/disorders, such as relieving edema and rheumatism pain, treating cough and asthma, treating enuresis, astringent urine and beriberi edema, purging blood and damp heat, and dispelling wind evil and dampness, etc. 48 compounds have been isolated from Fangji, belonging to alkaloids, flavonoids, and steroids, other compounds. The crude extracts and isolated compound of Fangji have shown a wide range of pharmacological activities, such as anti-tumor, anti-inflammatory, and neuroprotective activities, as well as role in reoxygenation, and antimicrobial effect, etc. Moreover, qualitative and quantitative analyses of quality control are reviewed, including qualitative analyses for the identification of compounds, as well as fingerprint and quantitative analyses by high performance liquid chromatography (HPLC) and capillary electrochromatography (CE). In the toxicity study, the hepatotoxicity, hepatorenal toxicity, nephrotoxicity, subacute and acute toxicities of the alcohol extract and water extract of Fangji, and tetrandrine were studied in-vitro and in-vivo experiments. CONCLUSION: In the history of uses, Fangji can be used to treat a variety of diseases, most of which are manifested in removing wind and dampness. In recent years, the phytochemistry of Fangji has rarely been reported. The pharmacological activities of Fangji mainly focus on the compounds, tetrandrine and fangchinoline, and there are a few reports on the pharmacological studies of other compounds in Fangji. Moreover, the quality control of Fangji lacks a standard fingerprint to distinguish Fangji from other easily-confused medicinal materials. In the toxicity study, there is no report on the mechanism of toxicity research. Therefore, further studies on such mechanisms are needed.

Circulating MiR-29a, Possible Use as a Biomarker for Monitoring IgA Nephropathy.

INTRODUCTION: Previous studies have shown that TGF-ß1/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. To date, only few studies have reportedon circulating microRNAs in IgA nephropathy (IgAN). However, the plasma expression of miR-29a and its role in patients with IgAN remains unclear. In this study, we attempted to elucidate whether plasma miR-29a expression can be used as a biomarker for monitoring disease states. METHODS: For this study, 15 healthy subjects, 36 patients with untreated renal biopsy-proven IgAN, and 79 patients with IgAN, who were under treatment for a period of 1 year on an average, all of whom had similar age and gender distributions, were included. The plasma expression of miR-29a in each group was explored by real-time PCR, and the relationship between miR-29a expression and clinical, pathological, and prognostic indicators of IgAN was further evaluated. RESULTS: Relative plasma expression of miR-29a in patients with IgAN was significantly lower than that in healthy controls (P < .001), and these changes in plasma miR-29a could be suppressed by treatment (P < .05). Plasma miR-29a was positively correlated with eGFR and negatively correlated with proteinuria and serum creatinine, irrespective of whether or not the patients with IgAN accepted treatment (P < .05). Plasma miR-29a level was negatively correlated with primary pathological parameters such as crescent formation, Lee's and Oxford classification (P < .05). Kaplan-Meier analysis revealed that patients with high plasma expression of miR-29a had better renal function and better response to treatment compared to those with low expression (P < .05). CONCLUSION: Plasma miR-29a could be considered as a biological marker that reflects renal damage and function, to predict the progression of IgAN.

The protective effect of Cordycepin on diabetic nephropathy through autophagy induction in vivo and in vitro.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious chronic complications of diabetes mellitus (DM). Autophagy is an important physiological function for podocytes to maintain stability of intracellular environment. In this study, we planned to clarify the effect of Cordycepin, a traditional Chinese medicine, on DN and the related mechanisms. METHODS: All rats were randomly divided into normal control group, diabetic controls, low-dose group (10 mg/kg), medium-dose group (100 mg/kg), and high-dose group (500 mg/kg). The level of cholesterol, blood sugar, triglyceride, creatinine, and urine protein was examined through an automatic biochemistry analyser. Enzyme-linked immunosorbent assay (Elisa) was used to detect the level of IL-1ß, IL-6, and IL-18. HE staining was used to examine histopathologic changes. TUNEL staining was used to detected cell apoptosis. The expression of fibrosis markers α-SMA, t-TG, and TIMP-1, apoptosis-related proteins cleaved-caspase3, Bax and Bcl-2, autophagy markers Beclin1, light chain 3 (LC3)I/II, and p62 were evaluated by western blot. RESULTS: The level of cholesterol, blood sugar, triglyceride, creatinine, and urine protein in the diabetic controls was much higher than that in the normal control group. Obvious histopathology injuries were also found in DN model group. After Cordycepin treatment, all the above indexes were improved compared with the DN group and tissue damages were also alleviated. Further studies showed that Cordycepin suppressed cell apoptosis and renal fibrosis and rescued cell autophagy in DN rat model. Moreover, the results of our in vitro experiments showed that the addition of 3-methyladenine (3-MA, specific autophagy inhibitor) successfully abolished the protective effect of Cordycepin on renal fibrosis through inducing apoptosis and renal fibrosis. The above protective effects of Cordycepin were exhibited in a dose-dependent manner. CONCLUSION: Cordycepin participated in the modulation of cell apoptosis, fibrosis, and autophagy induction in DN. Our study for the first time revealed that Cordycepin had a certain therapeutic effect on DN in rats through autophagy induction.