Homeopathic Formulations of Syzygium jambolanum Alleviate Glycation-Mediated Structural and Functional Modifications of Albumin: Evaluation through Multi-Spectroscopic and Microscopic Approaches.

BACKGROUND: The growing interest in identifying the mode of action of traditional medicines has strengthened its research. Syzygium jambolanum (Syzyg) is commonly prescribed in homeopathy and is a rich source of phytochemicals. OBJECTIVE: The present study aims to shed light on the anti-glycation molecular mechanism of Syzyg mother tincture (MT), 30c, and 200c on glycated human serum albumin (HSA) by multi-spectroscopic and microscopic approaches. METHODS: The phytochemicals and antioxidant potential of the Syzyg formulations were estimated by the high-performance liquid chromatography and spectroscopic technique, respectively. Glycation was initiated by incubating HSA with methylglyoxal, three Syzyg formulations, and the known inhibitor aminoguanidine in separate tubes at 37°C for 48 hours. The formation of glycation adducts was assessed by spectrofluorometer and affinity chromatography. The structural modifications were analyzed through circular dichroism, Fourier transform infrared spectroscopy, turbidity, 8-anilinonapthalene-1-sulfonic acid fluorescence, and nuclear magnetic resonance. Further, the formation of the aggregates was examined by thioflavin T, native-polyacrylamide gel electrophoresis, and transmission electron microscopy. Additionally, the functional modifications of glycated HSA were determined by esterase-like activity and antioxidant capacity. The binding analysis of Syzyg formulations with glycated HSA was evaluated by surface plasmon resonance (SPR). RESULTS: Syzyg formulations MT, 30c, and 200c contained gallic acid and ellagic acid as major phytochemicals, with concentrations of 16.02, 0.86, and 0.52 µg/mL, and 227.35, 1.35, and 0.84 µg/mL, respectively. Additionally, all three formulations had remarkable radical scavenging ability and could significantly inhibit glycation compared with aminoguanidine. Further, Syzyg formulations inhibited albumin's structural and functional modifications. SPR data showed that Syzyg formulations bind to glycated HSA with an equilibrium dissociation constant of 1.10 nM. CONCLUSION: Syzyg formulations inhibited the glycation process while maintaining the structural and functional integrity of HSA.

The interaction on HSA and the antibacterial activity from four polyoxometalate hybrids based on berberine.

Four organic-polyoxometalate hybrids BR4[SiW12O40] (BR-SiW), BR3[PMo12O40] (BR-PMo), BR4K[EuSiW11O40]·2H2O (BR-EuSiW) and BR6Na3[EuW10O36] (BR-EuW) were fabricated by the polyoxometalates (POMs) anions and berberine cations (BR) noted for the alkaloids in traditional Chinese herbal medicine. These hybrids have been characterized and confirmed. The interaction between hybrids and human serum albumin (HSA) was investigated in a buffer solution (pH 7.4) using ultraviolet-visible light absorption and fluorescence techniques. The classical Stern-Volmer equation was used to analyze the fluorescence quenching at three temperatures (296, 303 and 310 K), and the static quenching mechanism for interaction was proposed. The Thermodynamic parameters, enthalpy, entropy change, and Gibbs free energy of hybrids interacting on HSA were calculated by Scatchard equation. The results indicated that therewas one binding site on the protein and BR-POMs all showed stronger binding force than that of raw materials. Synchronous fluorescence results showed that the binding sites of BR-POMs and HSA were not effectively affected the surrounding microenvironment. The following antibacterial experiments implied that inhibitory effect of hybrids were synergistic effect from organic active ingredient and POMs but the simple combination. All these data were prepared for further research on biology.

Effect of intradialytic oral nutritional supplementation on nutritional markers in malnourished chronic hemodialysis patients: prospective randomized trial.

BACKGROUND AND OBJECTIVES: Malnutrition is prevalent in chronic hemodialysis (HD) patients. It increases mortality and negatively affects quality of life. This study aimed to assess the effect of intradialytic oral nutritional supplement (ONS) on nutritional markers in chronic HD patients with protein energy wasting (PEW). METHODS: This 3-month prospective, open-label, randomized controlled trial included 60 chronic HD patients with PEW. The intervention group (30 patients) received intradialytic ONS and dietary counseling, whereas the control group (30 patients) received only dietary counseling. Nutritional markers were measured at the beginning and end of the study. RESULTS: The mean age of the patients was 54 ± 12.7 years, and that of the HD vintage was 64 ± 49.3 months. Compared to the control group, the intervention group showed a significant increase in serum albumin (p < 0.001), prealbumin (p < 0.001), cholesterol (p = 0.016), body mass index (BMI) (p = 0.019), serum creatinine/body surface area (BSA) (p = 0.016), and composite French PEW score (p = 0.002), as well as a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (p = 0.001). The total iron binding capacity, normalized protein nitrogen appearance, and hemoglobin levels increased significantly in both groups. CONCLUSION: Intradialytic ONS and dietary counseling for three months were more effective than dietary counseling alone in terms of improving nutritional status and inflammation in chronic HD patients, as evidenced by increases in serum albumin, prealbumin, BMI, serum creatinine/BSA, composite French PEW score, and a decrease in hs-CRP.

Impact of Vitamin D3 on Carbonyl-Oxidative Stress and Matrix Metalloproteinases after Acute Intracerebral Hemorrhage in Rats with Type 2 Diabetes Mellitus.

INTRODUCTION: Diabetes mellitus is associated with the development of carbonyl-oxidative stress (COS) and an increased risk of a cerebral hemorrhage. Vitamin D3 is considered an additional drug to have an impact on COS and proteolysis in the extracellular matrix. OBJECTIVE: The study aimed to evaluate the impact of D3 on the COS-markers and matrix metalloproteinases MMP2/MMP9 activity after acute intracerebral hemorrhage (ICH) in rats with experimental type 2 diabetes mellitus (Т2DM) compared to metformin (Met). METHODS: T2DM was induced in rats via the intraperitoneal injection of streptozotocin (STZ) and nicotinamide (NA), ICH - by microinjection of bacterial collagenase into the striatum. Rats were randomized into five groups: 1 - intact animals (n = 8), 2 - T2DM (n = 9); 3 - T2DM+ICH (n = 7); 4 - T2DM+ICH+Met (n = 7); 5 - T2DM+ICH+D3 (n = 7). Blood glucose, glycated hemoglobin, and oral glucose tolerance test (OGTT) were assessed using commercial kits. Advanced oxidation protein products (AOPP), protein carbonyls (PC370/430), and ischemia-modified albumin (IMA) were measured by spectrophotometry, advanced glycation end products (AGEs) by quantitative fluorescence, and matrix metalloproteinases MMP2/9 by gelatin zymography. RESULTS: D3 does not significantly affect the glucose level and OGTT in rats with T2DM+ICH. However, it reduces AOPP, PC, and AGEs, thus reducing the COS index. In contrast, the activity of proMMP9 increases after D3 administration. These effects of D3 have been reported to be stronger and sometimes opposite to those of metformin. CONCLUSION: D3 supplementation may decrease the negative consequences of a cerebral hemorrhage in T2DM by reducing COS and preventing the accumulation of COS-modified proteins in the brain by regulating the expression and activity of MMP9.

High Protein Whole Food Snack and Albumin Outcomes in Patients With Dialysis-Dependent Chronic Kidney Disease.

OBJECTIVE: Protein-energy wasting is common among patients on hemodialysis (HD). This study sought to define effects that a novel, post-HD, high-calorie, high-protein whole food snack had on patients' serum albumin (serum alb), serum phosphorus and equilibrated normalized protein catabolic rate (enPCR). METHODS: A 12-month (6 months intervention, 6 months pre/post data collection), single-center, unblinded study was conducted. Participants (n = 67) consumed, ad libitum, a whole food snack post-HD for 6 treatments each month. Upon analysis, regression models identified relationships between serum alb and whole food snack consumption across follow up. Predefined effect size anticipated was + 0.2 g/dL. Patients were stratified by high (≥4 g/dL) or low (<4 g/dL) mean serum alb during a 3-month baseline period. Paired t-tests compared mean per patient difference in serum alb, enPCR and serum phosphorus from baseline to each month of follow up, stratified by high (≥640 g) or low (<640 g) consumption of the whole food snack (a priori caloric estimation). RESULTS: Linear regression models showed positive associations between higher serum alb and enPCR with higher whole food snack consumption across follow up (all P < .05). Assessments from baseline to each follow-up month show some increases in serum alb, yet t test comparisons were not significant. No significant changes were seen in serum phosphorus levels during follow-up. CONCLUSION: Albeit the catabolic effects of HD are well-known, effective nutritional interventions are scarce. Results showed that providing a whole food snack post-HD to individuals with serum alb <4.0 g/dL may be beneficial but further studies are recommended.

Tetrandrine Attenuates Podocyte Injury by Inhibiting TRPC6-Mediated RhoA/ROCK1 Pathway.

Tetrandrine (Tet), a compound found in a traditional Chinese medicine, presents the protective effect for kidney function. Our study is aimed at clarifying the efficacy and underlying mechanism of Tet on podocyte injury. In this study, podocyte injury was induced in rats with adriamycin (ADR), and MPC5 podocytes were constructed with TRPC6 overexpression. We found that Tet treatment reduced the levels of proteinuria, serum creatinine, and blood urea nitrogen and increased plasma albumin levels in ADR-induced rats. Tet reduced intracellular Ca2+ influx and apoptosis in MPC5 podocytes overexpressing TRPC6. Tet downregulated the expression of renal TRPC6, RhoA, and ROCK1 and upregulated the expression of synaptopodin; meanwhile, it reduced calcineurin activity in vivo and in vitro. In conclusion, Tet protects against podocyte by affecting TRPC6 and its downstream RhoA/ROCK1 signaling pathway.

The effect of riboflavin supplementation on the systemic redox status in healthy volunteers: A post-hoc analysis of the RIBOGUT trial.

BACKGROUND: Riboflavin is a redox-active vitamin that plays a pivotal role in human energy metabolism. Riboflavin may have beneficial health effects by increasing extracellular antioxidant capacity, thereby alleviating oxidative stress. Reduced levels of free thiols in blood reflect systemic oxidative stress, since they are readily oxidized by reactive species. In this study, we aimed to study the potential of riboflavin supplementation to improve the systemic redox status in healthy volunteers. METHODS: This study was a post-hoc analysis of the RIBOGUT study, a randomized, double-blind, placebo-controlled human intervention trial that investigated the effect of riboflavin supplements on the gut microbiota composition of healthy individuals. Serum free thiols were quantified before and after intervention and adjusted to serum albumin levels. Changes in albumin-adjusted free thiols were analyzed, as well as potential associations with routine laboratory parameters and faecal bacterial quantification by fluorescence in-situ hybridization (FISH). RESULTS: Participants were randomized to either placebo (n = 34), riboflavin 50 mg daily (n = 32), or riboflavin 100 mg daily (n = 33). At baseline, no significant differences in albumin-adjusted serum free thiols were observed. After intervention with either placebo or riboflavin, albumin-adjusted serum free thiols did not significantly change (P > 0.05), however, observed changes were inversely associated with changes in C-reactive protein (CRP) levels (r = -0.22, P < 0.05). At baseline, albumin-adjusted serum free thiols were positively associated with faecal relative abundances of Faecalibacterium prausnitzii (P < 0.01). CONCLUSION: Riboflavin did not change the systemic redox status in healthy individuals as reflected by serum free thiols, but observed changes in albumin-adjusted free thiol levels were negatively associated with changes in CRP levels. Strikingly, albumin-adjusted free thiols were independently associated with relative abundances of faecal F. prausnitzii, which may suggest a potential host redox-microbiota interaction.

Clinical Significance of Albumin- and Bilirubin-Based Biomarkers in Glaucoma: A Retrospective Case-Control Study.

Glaucoma is the second leading cause of global blindness. The etiology of glaucoma is complicated. In addition to elevated intraocular pressure (IOP), several other mechanisms have been implicated in pathogenesis, such as oxidative stress and systemic inflammation. Serum albumin (ALB) and bilirubin (BIL) have been reported to have potent antioxidant properties and contribute to maintain redox homeostasis in various diseases. However, associations between these parameters and glaucoma remain mostly unknown. Here, we conducted a retrospective case-control study, revealing that serum ALB, total BIL (TBIL), and indirect BIL (IBIL) levels were markedly lower in glaucoma patients than those in healthy controls. Furthermore, the neutrophil-to-ALB (NAR), neutrophil-to-TBIL (NTBR), and neutrophil-to-IBIL (NIBR) ratios were greatly higher in glaucoma. Additionally, interestingly, lower ALB and BIL levels and higher NAR, NTBR, and NIBR were associated with severer glaucomatous visual impairment, and NAR, NTBR, and NIBR showed good accuracy as diagnostic tests for glaucoma severity, suggesting these indices might be useful as discriminative biomarkers for disease severity. Our current findings demonstrate associations between ALB, BIL, NAR, NTBR, NIBL, and glaucoma. It might be useful to use NAR, NTBR, and NIBR as predictive markers for disease severity and employ ALB/BIL as alternative therapy or adjuvant medicines in glaucoma patients.

The Relation of Serum Dehydroepiandrosterone Sulfate Level to Protein Energy Wasting in Hemodialysis Patients.

Protein-energy wasting (PEW) is a major risk for morbidity and mortality in hemodialysis (HD) patients. The change in the concentration of dehydroepiandrosterone sulfate (DHEA-S) may play a role in PEW. The aim of this work was to study the possible relationship between serum DHEA-S levels and various nutritional and inflammatory parameters in a cohort of HD patients. In total, 78 HD patients (47 males and 31 females) were included in this crosssectional observational study. In addition to taking their history, clinical examinations, and routine laboratory investigations, the nutritional status was assessed, and their serum DHEA-S was measured. Nutritional status was assessed by anthropometric measures, bioelectrical impedance analysis, malnutrition inflammation scores, and subjective global assessments. A diagnosis of malnutrition was made based on the recommendations of the International Society of Renal Nutrition and Metabolism. The relationship between DHEA-S and various nutritional parameters was analyzed. Eighteen patients (23.1%) suffered from PEW. Those with PEW had a longer duration of HD (P = 0.04), and lower serum levels of creatinine (P = 0.003), hemoglobin (P = 0.01), albumin (P <0.0001), cholesterol (P = 0.02), and DHEA-S (P = 0.01). Among the variables, serum DHEA-S levels were significant predictors of PEW in this cohort (odds ratio: 0.976; 95% confidence interval: 0.954-1.0; P = 0.04). PEW is frequently encountered in HD patients. Decreased serum DHEA-S levels were associated with PEW in male HD patients. Further studies are needed to assess the effect of hormone supplementation on this serious disorder in HD patients.

Antiglycoxidative Properties of Extracts and Fractions from Reynoutria Rhizomes.

Hyperglycemia, when sustained over a long time in diabetes mellitus (DM), leads to biochemical and cellular abnormalities, primarily through the formation of advanced glycation end-products (AGEs). In the treatment of diabetes, beside blood-sugar-lowering medications, a consumption of herbal products that can inhibit the AGEs' formation is recommended. This study investigated the in vitro antiglycoxidative potential of extracts and fractions from the rhizomes of Japanese, Giant, and Bohemian knotweeds (Reynoutria japonica (Houtt.), R. sachalinensis (F. Schmidt) Nakai, and R.× bohemica Chrtek et Chrtkova). Their effects on glycooxidation of bovine and human serum albumin were evaluated by incubation of the proteins with a mixture of glucose and fructose (0.5 M) and 150 µg/mL of extract for 28 days at 37 °C, followed by measuring early and late glycation products, albumin oxidation (carbonyl and free thiol groups), and amyloid-ß aggregation (thioflavin T and Congo red assays). The highest antiglycoxidative activity, comparable or stronger than the reference drug (aminoguanidine), was observed for ethyl acetate and diethyl ether fractions, enriched in polyphenols (stilbenes, phenylpropanoid disaccharide esters, and free and oligomeric flavan-3-ols). In conclusion, the antiglycoxidative compounds from these three species should be further studied for potential use in the prevention and complementary treatment of DM.

Beneficial Effects of Oral Nutritional Supplements on Body Composition and Biochemical Parameters in Women with Breast Cancer Undergoing Postoperative Chemotherapy: A Propensity Score Matching Analysis.

Aim: Recently, more attention has been paid to the role of nutritional intervention in preventing the side effects of chemotherapy in oncology patients. Therefore, the aim of the present study was to analyze the effects of oral nutritional supplements on the body composition and biochemical parameters in women with breast cancer receiving postoperative adjuvant chemotherapy. Patients and Methods: The study involved women diagnosed with breast cancer who underwent surgical treatment and were qualified for chemotherapy (doxorubicin and cyclophosphamide). Women were divided into two groups, depending on whether oral nutritional supplements were used during chemotherapy. Anthropometric and biochemical parameters were analyzed twice in all patients: before and after six weeks of chemotherapy. Propensity score (PS) matching was performed to select patients balanced in terms of age, BMI, and clinicopathological features of the tumor. Statistical comparisons were conducted in a propensity-matched cohort of patients. Results: The value of BMI was maintained constant in the supplemented women older than 56 years after six weeks of chemotherapy. Regardless of age in the supplemented women, a significant increase in muscle mass, fat free mass (FFM), and fat free mass index (FFMI) was demonstrated. An increase in fat mass (FM) including visceral fat was observed only in the non-supplemented control. Regardless of age or initial FM, supplemented women exhibited a constant level of albumin. Moreover, in the supplemented women with normal initial FM, the stable values of triglycerides and HDL cholesterol were maintained after six weeks of chemotherapy. Conclusion: The present study demonstrated that oral nutritional supplements could improve body composition and prevent hypoalbuminemia and lipid abnormalities in women with breast cancer undergoing chemotherapy.

Protective Effect of Opuntia dillenii (Ker Gawl.) Haw. Seed Oil on Gentamicin-Induced Nephrotoxicity: A Biochemical and Histological Analysis.

Opuntia dillenii is a medicinal plant with frequent usage in folk medicine to treat many illnesses. The present study aims to investigate the protective effect of Opuntia dillenii seed oil against gentamicin-induced nephrotoxicity in rats. The animals (rats) were randomly divided into three groups (i) the normal control group treated only with distilled water (10 mL/kg), (ii) the gentamicin group treated with distilled water (10 mL/kg) and received an intraperitoneal injection of gentamicin (80 mg/kg), and (iii) the group treated with the Opuntia dillenii seed oil (2 mL/kg) and also received an intraperitoneal injection of gentamicin (80 mg/kg). The rats received their following treatments for 14 consecutive days orally. Serum urea, creatinine, gamma-glutamyl transferase, albumin, and electrolyte levels were quantified as the markers of acute renal and liver failure. Besides, the kidney and liver relative weight, kidney malondialdehydes, and kidney histological analysis were determined. The results have shown that daily pretreatment with Opuntia dillenii seed oil (2 mL/kg) prevented severe alterations of biochemical parameters and disruptions of kidney tissue structures. In addition, the results of the present study showed for the first time that Opuntia dillenii seed oil reduced renal toxicity in gentamicin-induced nephrotoxicity in rats. Therefore, Opuntia dillenii seed oil may represent a new therapeutic avenue to preserve and protect renal function in gentamicin-treated patients.

Effects of antioxidant supplementation on oxidative stress balance in young footballers- a randomized double-blind trial.

BACKGROUND: Intensive physical exercise that competitive sports athletes participate in can negatively affect their pro-oxidative-antioxidant balance. Compounds with high antioxidant potential, such as those present in chokeberry (Aronia melanocarpa), can prevent these adverse changes. We here investigated the effect of antioxidant supplementation on oxidative stress balance in young footballers. METHODS: The study was designed as a double-blind randomized trial. Diet of a group of young football players (male; n = 20; mean age, 15.8 years-old) was supplemented with 200 ml of chokeberry juice per day, for 7 weeks. The players were randomly assigned to the experimental (supplemented, FP-S; n = 12) and control (placebo, FB-C; n = 8) groups. Before and after the supplementation period, the participants performed a beep test. Venous blood was sampled for serum analysis before, immediately after, 3 h, and 24 h after the beep test. Serum levels of thiobarbituric acid reactive products, 8-hydroxy-2'-deoxyguanosine, total antioxidant capacity, iron, hepcidin, ferritin, myoglobin, and albumin, and morphological blood parameters (red blood cells, (RBC), haemoglobin (HGB), haematocrit (HCT) mean corpuscular volume (MCV) mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and lactic acid) were determined. RESULTS: Chokeberry juice supplementation did not significantly affect the outcome of the beep test. The supplementation did not significantly affect any of the morphological, biochemical, or performance parameters analysed. CONCLUSIONS: Chokeberry juice supplementation did not affect the measured parameters in the studied population, which may indicate insufficient antioxidant capacity of the juice.

Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons.

Nowadays, it is accepted that the regular practice of exercise and branched-chain amino acids supplementation (BCAAs) can benefit the immune responses in older persons, prevent the occurrence of physical frailty (PF), cognitive decline, and aging-related comorbidities. However, the impact of their combination (as non-pharmacological interventions) in albumin and the inflammatory markers is not fully understood. Therefore, we investigated the effect of a 40-week multifactorial intervention [MIP, multicomponent exercise (ME) associated or not with BCAAs] on plasma levels of inflammatory markers and albumin in frail older persons (≥75 years old) living at residential care homes (RCH). This study consisted of a prospective, naturalistic, controlled clinical trial with four arms of multifactorial and experimental (interventions-wahshout-interventions) design. The intervention groups were ME + BCAAs (n = 8), ME (n = 7), BCAAs (n = 7), and control group (n = 13). Lower limb muscle-strength, cognitive profile, and PF tests were concomitantly evaluated with plasma levels of albumin, anti- and pro-inflammatory cytokines [Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) respectively], TNF-α/IL-10 ratio, and myeloperoxidase (MPO) activity at four different time-points: Baseline (T1), after 16 weeks of multifactorial intervention (T2), then after a subsequent 8 weeks washout period (T3) and finally, after an additional 16 weeks of multifactorial intervention (T4). Improvement of cognitive profile and muscle strength-related albumin levels, as well as reduction in the TNF-α levels were found particularly in ME plus BCAAs group. No significant variations were observed over time for TNF-α/IL-10 ratio or MPO activity. Overall, the study showed that MIP triggered slight alterations in the inflammatory and physical function of the frail older participants, which could provide independence and higher quality of life for this population.

Methods and Nutritional Interventions to Improve the Nutritional Status of Dialysis Patients in JAPAN-A Narrative Review.

Patients receiving dialysis therapy often have frailty, protein energy wasting, and sarcopenia. However, medical staff in Japan, except for registered dietitians, do not receive training in nutritional management at school or on the job. Moreover, registered dietitians work separately from patients and medical staff even inside a hospital, and there are many medical institutions that do not have registered dietitians. In such institutions, medical staff are required to manage patients' nutritional disorders without assistance from a specialist. Recent studies have shown that salt intake should not be restricted under conditions of low nutrition in frail subjects or those undergoing dialysis, and protein consumption should be targeted at 0.9 to 1.2 g/kg/day. The Japanese Society of Dialysis Therapy suggests that the Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) is a useful tool to screen for older patients with malnutrition.

Efficacy and safety of astragalus injection combined with Western medicine in the treatment of early diabetic nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes. Its clinical manifestation is proteinuria, and it is a common cause of renal failure. At present, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists are often used to treat early DN, and they have good curative effect. On this basis, the treatment of early DN with the combination of astragalus injection is becoming more and more widespread. Therefore, the purpose of this study is to prove the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN, and to provide reference value for clinical practice in the future. METHODS: English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructur, Wanfang, VP Information Chinese Journal Service Platform, China Biology Medicine disc) will be searched by computer. From the establishment of the database to February 2021, a randomized controlled trial of astragalus injection combined with Western medicine in the treatment of early DN will be conducted. Two researchers independently evaluate the quality of the included study and extract the data. Included literature is analyzed by Meta with RevMan5.3 software. RESULTS: In this study, the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN are evaluated by serological indexes such as Urinary albumin excretion rates (UAER), serum creatinine and blood urea nitrogen, as well as the adverse reactions of drugs. CONCLUSION: This study will provide reliable evidence-based evidence for astragalus injection combined with Western medicine for the treatment of early DN. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/A9JGP.

In vivo assessment of reversing aminoglycoside antibiotics nephrotoxicity using Jatropha mollissima crude extract.

Aminoglycoside antibiotics are widely employed clinically due to their powerful bactericidal activities, less bacterial resistance compared to beta lactam group and low cost. However, their use has been limited in recent years due to their potential induction of nephrotoxicity. Here we investigate the possibility of reversing nephrotoxicity caused by gentamicin in rat models by using ethanolic crude extract of the medicinal plant Jatropha Mollissima. Nephrotoxic male Wistar rats was obtained by gentamicin antibiotic, which then treated with two doses of J. mollissima crude extract for 3 weeks with monitoring their parameter in weekly base. Our results indicate that J. mollissima crude extract at both doses has strong protection ability against gentamicin nephrotoxicity, most of tested parameters backed to normal values after few days from the administration of the crude extract, which could be due to the antagonized the biochemical action of gentamicin on the proximal tubules of the kidney. The results of histopathologic analysis showed observable improvement in J. mollissima treated groups compared with untreated groups. Our findings suggests the J. mollissima has exceptional nephron protection potentials able to reverse the nephrotoxicity caused by gentamicin antibiotic.

Expanding the Cross-Link Coverage of a Carboxyl-Group Specific Chemical Cross-Linking Strategy for Structural Proteomics Applications.

Carboxyl-group specific chemical cross-linking is gaining an increased interest as a structural mass spectrometry/structural proteomics technique that is complementary to the more commonly used amine-specific chemistry using succinimide esters. One of these protocols uses a combination of dihydrazide linkers and the coupling reagent DMTMM [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium] chloride, which allows performing the reaction at neutral pH. The reaction yields two types of products, carboxyl-carboxyl cross-links that incorporate the dihydrazide linker and zero-length carboxyl-amine cross-links induced by DMTMM alone. Until now, it has not been systematically investigated how the balance between the two products is affected by experimental conditions. Here, we studied the role of the ratios of the two reagents (using pimelic dihydrazide and DMTMM) and demonstrate that the concentration of the two reagents can be systematically adjusted to favor one reaction product over the other. Using a set of five model proteins, we observed that the number of identified cross-linked peptides could be more than doubled by a combination of three different reaction conditions. We also applied this strategy to the bovine 20S proteasome and the Escherichia coli 70S ribosome, again demonstrating complementarity and increased cross-link coverage.

Antitumor and antioxidant activities of purple potato ethanolic extract and its interaction with liposomes, albumin and plasmid DNA.

The aim of the study was to broadly determine the biological activities of purple potato ethanolic extract of the Blue Congo variety (BCE). The antioxidant activity of BCE was determined in relation to liposome membranes, and peroxidation was induced by UVB and AAPH. To clarify the antioxidant activity of BCE, we investigated its interactions with hydrophilic and hydrophobic regions of a membrane using fluorimetric and FTIR methods. Next, we investigated the cytotoxicity and pro-apoptotic activities of BCE in two human colon cancer cell lines (HT-29 and Caco-2) and in normal cells (IPEC-J2). In addition, the ability to inhibit enzymes that are involved in pro-inflammatory reactions was examined. Furthermore, BCE interactions with serum albumin and plasmid DNA were investigated using steady state fluorescence spectroscopy and a single molecule fluorescence technique (TCSPC-FCS). We proved that BCE effectively protects lipid membranes against the process of peroxidation and successfully inhibits the cyclooxygenase and lipoxygenase enzymes. Furthermore, it interacts with the hydrophilic and hydrophobic parts of lipid membranes as well as with albumin and plasmid DNA. It was observed that BCE is more cytotoxic against colon cancer cell lines than normal IPEC-J2 cells; it also induces apoptosis in cancer cell lines, but does not induce cell death in normal cells.

The isolation of secondary metabolites from Rheum ribes L. and the synthesis of new semi-synthetic anthraquinones: Isolation, synthesis and biological activity.

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Iskin" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, ß-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the NαFmoc-l-Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with NαFmoc-l-Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the NαFmoc-l-Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from -7.30 and -10.62 kcal/mol.