Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species.

The aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

Short-term steaming during processing impacts the quality of Citri Reticulatae 'Chachi' peel.

Citrus peel is a commonly used food-medicine material in the production of fast-moving consumer goods (FMCGs). For instance, Ganpu tea is manufactured by combining the peel of Citri Reticulatae 'Chachi' (PCRC) with Pu-erh tea. The alleviated irritation of PCRC through years of aging makes Citri reticulatae Pericarpium a traditional Chinese medicine. Herein, we introduced short-term steaming into the processing of PCRC to favor the quick removal of its irritation while retaining its food-medicine properties. Sensory evaluation and volatile component analysis showed that 60-s steaming reduced irritation of freshly prepared PCRC. Biological evaluations indicated no effects of steaming on the neuroprotective activity of PCRC. The process increased the contents of several bioactive ingredients, including hesperidin, nobiletin, tangeretin, and synephrine. In addition, physical indications of accelerating PCRC aging were observed. Taken together, our findings suggest that short-term steaming may offer a promising new possibility for enhancing the quality of citrus peel.

Causal associations of plasma omega-3 polyunsaturated fatty acids with sarcopenia-related traits: a two-sample Mendelian randomization study.

OBJECTIVE: To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach. METHODS: Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP). RESULTS: In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.375; left leg: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.446; right arm: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.376; left arm: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.384; trunk:ß = 0.02, 95% CI = -0.02 to 0.06, P = 0.283; whole: ß = 0.01, 95% CI = -0.03 to 0.04, P = 0.631), grip strength (right hand: ß = -0.01, 95% CI = -0.03 to 0.01, P = 0.387; left hand: ß = -0.01, 95% CI = -0.02 to 0.01, P = 0.553) and walking pace (ß = 0.00, 95% CI = -0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association. CONCLUSIONS: Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits.

Tibetan tea consumption prevents obesity by modulating the cellular composition and metabolic reprogramming of white adipose tissue.

Obesity, a global health concern, is linked with numerous metabolic and inflammatory disorders. Tibetan tea, a traditional Chinese beverage rich in theabrownin, is investigated in this study for its potential anti-obesity effects. Our work demonstrates that Tibetan tea consumption in C57BL/6J mice significantly mitigates obesity-related phenotypic changes without altering energy intake. Computational prediction revealed that Tibetan tea consumption reconstructs gene expression in white adipose tissue (WAT), promoting lipid catabolism and thereby increasing energy expenditure. We also note that Tibetan tea suppresses inflammation in WAT, reducing adipocyte hyperplasia and immune cell infiltration. Furthermore, Tibetan tea induces profound metabolic reprogramming, influencing amino acid metabolic pathways, specifically enhancing glutamine synthesis, which in turn suppresses pro-inflammatory chemokine production. These findings highlight Tibetan tea as a potential candidate in obesity prevention, providing a nuanced understanding of its capacity to modulate the cellular composition and metabolic landscape of WAT.

Quality evaluation of Pterocephali Herba through simultaneously quantifying 18 bioactive components by UPLC-TQ-MS/MS analysis.

Pterocephali Herba (PH), the dried whole plant of Pterocephalus hookeri, is a Tibetan medicine commonly used to treat rheumatoid arthritis (RA). Iridoids, triterpenoids, flavonoids and phenylpropanoids are the major groups of bioactive constituents from PH. However, only ursolic acid and oleanolic acid, two unspecific triterpenoid components, are used as markers for the quality control of PH in Chinese Pharmacopoeia. Herein, an UPLC-TQ-MS/MS integrating SIR and MRM mode method for simultaneously quantifying 18 components, i.e., 9 iridoids, 3 triterpenoids, 3 phenylpropanoids, 2 flavonoids and quinic acid, in PH was developed and validated, and was used to evaluate 10 batches of PH samples from different origins. Hierarchical cluster analysis (HCA) was used to show the clustering of PH samples, while spearman correlation analysis was adopted to evaluate the correlation between ursolic acid/oleanolic acid and other quantified components. It was found that the established method was sensitive, precise, and accurate enough for the simultaneous quantification of 18 analytes in PH samples. Significant differences were found among the contents of 18 components in PH samples, no apparent clustering of the quality of PH samples was found to be related to its origins, and the contents of ursolic acid/oleanolic acid were only significantly correlated to the content of sylvestroside I, dipsanoside B, dipsanoside A in PH. Our results suggested that the newly established multi-components quantitative method is an improved approach for quality evaluation of PH samples. Furthermore, the holistic quality was inconsistent among PH samples, and ursolic acid/oleanolic acid alone could not indicate the holistic quality variation trend of PH.

Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia.

The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

Aflatoxin B1 damaged structural barrier through Keap1a/Nrf2/ MLCK signaling pathways and immune barrier through NF-κB/ TOR signaling pathways in gill of grass carp (Ctenopharyngodon idella).

Aquafeeds are susceptible to contamination caused by aflatoxin B1 (AFB1). The gill of fish is an important respiratory organ. However, few studies have investigated the effects of dietary AFB1 exposure on gill. This study aimed to discuss the effects of AFB1 on the structural and immune barrier of grass carp gill. Dietary AFB1 increased reactive oxygen species (ROS) levels, protein carbonyl (PC) and malondialdehyde (MDA) contents, which consequently caused oxidative damage. In contrast, dietary AFB1 decreased antioxidant enzymes activities, relative genes expression (except MnSOD) and the contents of glutathione (GSH) (P < 0.05), which are partly regulated by NF-E2-related factor 2 (Nrf2/Keap1a). Moreover, dietary AFB1 caused DNA fragmentation. The relative genes of apoptosis (except Bcl-2, McL-1 and IAP) were significantly upregulated (P < 0.05), and apoptosis was likely upregulated through p38 mitogen-activated protein kinase (p38MAPK). The relative expressions of genes associated with tight junction complexes (TJs) (except ZO-1 and claudin-12) were significantly decreased (P < 0.05), and TJs were likely regulated by myosin light chain kinase (MLCK). Overall, dietary AFB1 disrupted the structural barrier of gill. Furthermore, AFB1 increased gill sensitivity to F. columnare, increased Columnaris disease and decreased the production of antimicrobial substances (P < 0.05) in grass carp gill, and upregulated the expression of genes involved with pro-inflammatory factors (except TNF-α and IL-8) and the pro-inflammatory response partly attributed to the regulation by nuclear factor κB (NF-κB). Meanwhile, the anti-inflammatory factors were downregulated (P < 0.05) in grass carp gill after challenge with F. columnare, which was partly attributed to the target of rapamycin (TOR). These results suggested that AFB1 aggravated the disruption of the immune barrier of grass carp gill after being challenge with F. columnare. Finally, the upper limit of safety of AFB1 for grass carp, based on Columnaris disease, was 31.10 µg/kg diet.

Effect of hydroxypropyl-ß-cyclodextrin and lecithin co-stabilized nanoemulsions on the konjac glucomannan/pullulan film.

In this study, the various ratio of hydroxypropyl-ß-cyclodextrin (HPCD) to lecithin (LEC) was 0:1, 0.5:1, 1:1, 1.5:1 and 2:1 (w/w) co-stabilized cinnamon essential oil (CEO) nanoemulsions were prepared. These nanoemulsions were successfully incorporated in the konjac glucomannan/pullulan polysaccharides-based film matrix. The composition of nanoemulsions and the effect of various nanoemulsions on rheological, mechanical, Water vapor permeability, optical, color, morphology properties, and CEO retention rate of the composite films were characterized. The results demonstrated that HPCD and LEC nanoemulsions had small particle size under 120 nm and high stability during 21 days storage, the incorporation of nanoemulsions reduced the viscosity of film-solution, transmittance, Water vapor permeability and mechanical properties of films, but an appropriate HPCD content 1:1 w/w of nanoemulsions could restored the mechanical properties of the films. Otherwise, 1:1 w/w of nanoemulsion film also exhibited a more compact and uniform structure, Furthermore, 2:1 w/w of nanoemulsion films with high retention rate of CEO, and the antioxidant and better antibacterial activities against E. coli and S. aureus. The nanoemulsion films utilized in this study also prolonged the shelf life of Agaricus bisporus mushrooms and cherries while maintaining their commercial value.

In vitro simulated digestion of and microbial characteristics in colonic fermentation of polysaccharides from four varieties of Tibetan tea.

Polysaccharides as a functional prebiotic have numerous activities such as regulating intestinal microorganisms and polysaccharide is one of the functional active components in tea has been known. In this study, we aimed to investigate the physicochemical characteristics of polysaccharides from four kinds of Tibetan teas at simulated digestion stages and the effect on the microbiota of fecal fermentation stages in vitro. The results revealed that Tibetan tea polysaccharides were partially digested during digestion. Additionally, during in vitro fecal microbial fermentation, Tibetan tea polysaccharides can promote the growth of some beneficial bacteria such as Bifidobacterium, Prevotella and Phascolarctobacterium to change the composition of intestinal microorganisms and promote the production of short-chain fatty acids (SCFAs). Finally, a strong correlation was found between the production of SCFAs and microorganisms including Bacteroides, Bifidobacterium and Lachnoclostridium. These results suggest that Tibetan tea polysaccharides could be developed as a prebiotic to regulate human gut microbiota.

[Intervention effect of Jingfang Mixture on urticaria mice based on NF-κB/NLRP3/IL-1ß signaling pathway].

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1ß were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1ß proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1ß and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1ß positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1ß protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1ß signaling pathway.

Dietary tea seed saponin combined with aerobic exercise attenuated lipid metabolism and oxidative stress in mice fed a high-fat diet (HFD).

Tea seed saponins (TSS) are oleanolane-type pentacyclic triterpenoid saponin mixtures with various pharmacological effects. We aimed to explore the effects of a total of 4 weeks intragastric administration of TSS (140 mg/kg·day) combined with aerobic exercise (AE) on lipid metabolism and its associated oxidative stress in HFD-induced obese mice and to investigate the possible molecular mechanisms. TSS + AE intervention significantly reduced body weight and the adiposity index (including subcutaneous, epididymal, perirenal, and abdominal adipose) in obese mice; improved dyslipidemia by lowering serum TC, TG, and LDL-c levels; and increased HDL-c levels. TSS + AE intervention significantly improved hepatic steatosis by inhibiting lipogenetic Acc, Srebp1c, and Scd1 and upregulating lipolysis genes (Pgc1α, Pgc1ß, Pparα, and Cpt1). TSS + AE intervention increased the hepatic protein expression of p-AMPK, SIRT1, and PGC-1α, as well as PPAR-γ and GLUT-4 in skeletal muscle compared with expression in the HFD group. In addition, TSS + AE also modulated oxidative stress in obese mice, which was indicated by the increased serum and liver levels of SOD, GSH, and T-AOC and decreased ROS and MDA levels. These results suggest that TSS + AE intervention can reduce fat accumulation and improve HFD-induced lipid metabolism disorders and oxidative stress. PRACTICAL APPLICATIONS: Obesity is a metabolic disease induced by excess nutritional intake and insufficient energy expenditure. Dietary modifications combined with aerobic exercise are currently an effective method for weight loss. Tea seed saponins (TSS) are a variety of biologically active oleanolane-type pentacyclic triterpenoid saponins that naturally exist in tea seeds. Few articles have focused on the effects and mechanisms of TSS combined with aerobic exercise (AE) in regulating lipid metabolism and improving oxidative damage in vivo. Using an HFD-induced obese mice model to explore the mechanism of TSS + AE in regulating lipid metabolism and its associated oxidative stress damage will help provide reliable data for the application of dietary nutrition combined with AE in anti-obesity.

Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study.

OBJECTIVE: Multiple observational studies have reported the close associations of obstructive sleep apnea (OSA) with serum uric acid (SUA) levels and gout. However, the causal nature and direction remains unclear. METHODS: A bidirectional two-sample Mendelian randomization (MR) study was performed, based on publicly available genome-wide association studies (GWAS) summary statistics, to investigate whether OSA is causally related to SUA levels, gout and vice versa. The inverse-variance weighted (IVW) was used as the primary analysis approach, supplemented with four sensitive analysis methods applied to assess the robustness of the results. Moreover, multivariable MR (MVMR) was utilized to evaluate the independent causal effect of OSA on SUA and gout after adjusting for body mass index (BMI), hypertension, type 2 diabetes (T2D), coronary artery disease (CAD), and chronic kidney disease (CKD). RESULTS: Genetically predicted OSA liability was significantly associated with increased levels of SUA (IVW method: ß = 0.19, 95% CI = 0.11 - 0.26, P = 7.24 × 10-7) and risk of gout [IVW method: odds ratio (OR) = 1.75 95% CI = 1.13 - 2.69, P = 0.01] in univariable MR. The MVMR results suggested that OSA retained its significant association with increased SUA levels, whereas the significant association between OSA and gout was attenuated to null after adjusting for BMI and T2D. No causal effect of OSA on SUA levels and gout was found in the reverse direction. CONCLUSIONS: Our findings suggest that OSA was causally associated with increased levels of SUA, but was not independently associated with gout risk.

Accurate 16S Absolute Quantification Sequencing Revealed Vaginal Microecological Composition and Dynamics During Mixed Vaginitis Treatment With Fufang FuRong Effervescent Suppository.

Background: The diagnosis and treatment of mixed vaginitis are more complicated than single pathogenic infections, and there may be adverse reactions and several contraindications to conventional antibiotic therapy. Therefore, this study aimed to evaluate the preliminary effects of Fufang Furong Effervescent Suppository for the management of aerobic vaginitis (AV) mixed with bacterial vaginosis (BV) using Accurate 16S absolute quantification sequencing (Accu16S). Methods: In the present randomized, blind, multi-center clinical trial, women (20 to 55 years) who had received a diagnosis of AV+BV were randomly assigned into clindamycin positive control (n = 41) and Fufang Furong Effervescent Suppository (n = 39) groups. The follow-up occurred in three time periods (V1: -2~0 days; V2: 15-17 days; V3: 40 ± 3 days). At each visit, two vaginal swabs, one for clinical evaluation and one for laboratory examination, were taken from each patient. The Nugent score, Donders' score, drug-related complications, recurrence rates, and microecological changes of vaginal swabs were assessed in the time three periods. Results: At baseline, the two groups were similar in frequency of presentation with vaginal burning, odor, abnormal discharge, and itching. No meaningful differences in Nugent and Donders' scores were detected between the two groups at stage V2 (Nugent: p = 0.67; Donders': p = 0.85) and V3 (Nugent: p = 0.97; Donders: p = 0.55). The Furong group presented fewer complications compared to the Clindamycin group. However, this difference was not statistically significant (p = 0.15). Additionally, Accu16S indicated that the total abundance of bacteria in both groups sharply decreased in stage V2, but slightly increased in V3. In stage V3, the absolute abundance of Lactobacillus in the Furong group was considerably higher compared to untreated samples (p < 0.05). On the other hand, no momentous increase was detected in the Clindamycin group (p > 0.05). Conclusion: Fufang Furong Effervescent Suppository can be as effective as clindamycin cream in the management of AV+BV while may restore the vagina microecosystem better.

Network Pharmacology and Pharmacological Mechanism of CV-3 in Atrial Fibrillation.

The high fatality and disability rate of atrial fibrillation (AF) strongly promote the development of pathogenesis and treatment of AF that is of great value. The present research attempted to clarify potential mechanisms of Mujiangzi oil (CV-3) in treating AF by constructing an AF cardiomyocytes model and using a network pharmacology approach. The experiment was divided into 4 groups: control, an AF model, AF + CV-3-treated, and the AF + verapamil group. Flow cytometry and the MTT assay were employed to detect cell apoptosis and cell viability, respectively. The main active components of CV-3 and predicted targets were obtained firstly, and molecular docking was performed. In the AF model, the cell apoptosis was aggravated, but inhibited in the CV-3-treated group. In addition, the cell viability was recovered after CV-3 treatment compared with the model group. Five potential active compounds of CV-3 were collected, including effective ingredients N-decanoic acid, spathulenol, copaene, ß-panasinsene, and eucalyptol. Among them, N-decanoic acid and spathulenol was demonstrated to bind to PTGS2 with binding energy of -4.08 and -7.09 kcal/mol, respectively, and hydrogen bonds interaction were found. The present study indicated that CV-3 could alleviate AF cardiomyocytes apoptosis and improve cardiomyocytes viability, and N-decanoic acid and spathulenol may be the key components of CV-3 in treatment of AF by regulating PTGS2. This study provided the possible target PTGS2 and the understanding of molecular mechanisms of CV-3 in treating AF.

Targeted and untargeted metabolomic analyses and biological activity of Tibetan tea.

Tibetan tea is not only a national product of geographical identity, but also a traditional beverage inherits Chinese tradition. This study evaluated the metabolic profiles and biological activity in four Tibetan teas. 83 non-volatile metabolites were identified as differentially expressed metabolites, including amino acids and their derivatives, phenolic acids, flavonoids, nucleotides and their derivatives, terpenes, alkaloids, organic acids, lipids and others. CC and 131 were rich in terpenoids and lipids. MZ contained the highest contents of amino acids and their derivatives, phenolic acids and flavonoids. 26 key volatile compounds were considered as odor-active compounds. MZ showed the highest level of antioxidant and hypoglycemic activity. Statistics analysis indicated that polyphenols, flavonoids and catechins were significantly correlated (|r| ≥ 0.7, P < 0.05) with biological activities. This study indicated significant differences in the metabolic profiles of various types of Tibetan tea, which provided a clear database for quality detection of Tibetan tea.

Biosynthesis-based spatial metabolome of Salvia miltiorrhiza Bunge by combining metabolomics approaches with mass spectrometry-imaging.

Defining the spatial distributions of metabolites and their structures are the two key aspects for interpreting the complexities of biosynthesis pathways in plants. As a means of obtaining information on the spatial distribution of metabolites, a strategy is needed that has high sensitivity and allows visualization. Toward this goal, we carried an untargeted metabolomics to obtain detailed metabolic information on different plant parts of Salvia miltiorrhiza, the roots of which are widely used in traditional Chinese medicine. Systematic optimization of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) including parameter selection and sample preparation were carried out to improve the sensitivity of the method for plant samples. Guided by the metabolomics data, the spatial distributions of diverse metabolites, including phenolic acids, flavonoids, tanshinones, carbohydrates, and lipids, were characterized and visualized for both the underground and aerial parts. To integrate the information pertaining to the spatial distribution of metabolites, the flavonoids and phenolic acids (phenylpropanoid metabolic pathway) were chosen as examples for in-depth study the biosynthesis pathways in S. miltiorrhiza. The complementary data obtained from the metabolomics study and mass spectrometry imaging enabled the identification of key reactions involved in flavonoid biosynthesis in flowers, which lead the changes in metabolite distribution. The analysis also identified the core precursor for phenolic acid biosynthesis in Salvia species. Therefore, the powerful combination of metabolomics and mass spectrometry imaging provides a basis for obtaining detailed information on spatial metabolome and constitutes a platform for deep understanding the biosynthesis of bioactive metabolites in plants.

Dietary proanthocyanidins alleviated ovarian fibrosis in letrozole-induced polycystic ovary syndrome in rats.

This study investigated the effects of proanthocyanidins (PCs) on ovarian fibrosis in letrozole-induced polycystic ovary syndrome (PCOS) in rats. The administration of PCs effectively reduced the body weight (BW) and relative ovarian weight in PCOS rats. ELISA results revealed that PCs significantly reduced the level of serum T, LH, LH/FSH in the PCOS group. In addition, qRT-PCR results revealed that treatment with PCs significantly increased the main antioxidant enzymes (Cat, Sod2, Gpx3, Mgst1, Gsta4, Sod1 and Prdx3) in PCOS rats. Also, the expression analysis of proteins by Western blotting revealed that PCs significantly decreased the level of TGF-ßR1, p-Smad3, p-Smad2 and Smad4 and reversed the downregulation of Smad7 in PCOS rats. The study suggested that PCs improved ovarian fibrosis in PCOS rats by regulating the serum hormone level, inhibiting oxidative stress and suppressing the activation of the TGF-ß1/Smads signaling pathway. PRACTICAL APPLICATIONS: Currently, plant extracts are being widely used to treat female reproductive and metabolic disorders. Particularly, proanthocyanidins (PCs), the well-known natural polyphenolic compounds, which are a significant source of antioxidants present in many colored fruits, are consumed as fruits as well as a dietary supplement to prevent many disorders. Recent pharmacological studies have reported that PCs have many health beneficial properties, such as antioxidant activity, improving cholesterol homeostasis, blood lipid regulatory properties, microcirculation improvement effect, antitumor activity and anti-aging activity. Despite these properties of PCs, the antifibrosis effect of PCs has not been studied to date. The main purpose of this study was to research the role and the mechanisms of PCs in ovarian fibrosis in PCOS rats.

Pharmacokinetics and Pharmacodynamics of Ceftolozane/Tazobactam in Critically Ill Patients With Augmented Renal Clearance.

OBJECTIVE: To determine whether established ceftolozane/tazobactam (C/T) dosing is adequate for patients with augmented renal clearance (ARC) and bacterial infection. METHODS: ARC (creatinine clearance [CrCl] ≥ 130 mL/min) was confirmed by directly measured CrCl in 11 critically ill patients in a phase 1 pharmacokinetics study. Patients received 3 g C/T (ceftolozane 2 g/tazobactam 1 g) as a 60-minute intravenous infusion. Pharmacokinetic sampling occurred at 0 (predose), 1, 2, 4, 6, and 8 hours after the start of the infusion. Noncompartmental analyses were conducted on concentration data. The following pharmacodynamic targets were evaluated: time that free (unbound) drug concentrations exceeded the minimum inhibitory concentration (fT>MIC) of 4 µg/mL for ceftolozane and time that the unbound concentration exceeded the 1 µg/mL target threshold (fT>threshold = 1 µg/mL) for > 20% of the dosing interval for tazobactam. Safety was evaluated. RESULTS: Mean (SD) area under the plasma concentration-time curve from 0 to infinity, clearance and volume of distribution at steady state (Vss) were 236 (118) h*µg/mL, 10.4 (4.5) L/h and 30.8 (10.8) L, respectively, for ceftolozane; and 35.5 (18.5) h*µg/mL, 35.3 (16.5) L/h and 54.8 (20.1) L, respectively, for tazobactam. Clearance and Vss were higher for both ceftolozane and tazobactam in patients with ARC compared with healthy individuals. The mean estimated ceftolozane fT>MIC at 4 µg/mL was 86.4%; the mean estimated tazobactam fT>threshold = 1 µg/mL was 54.9%. Treatment-emergent adverse events were mild to moderate. CONCLUSIONS: In patients with ARC, a 3 g C/T dose met respective pharmacodynamic targets for ceftolozane and tazobactam. CLINICALTRIALS. GOV IDENTIFIER: NCT02387372.

Efficacy and safety of modified Yupingfeng formula in treating allergic rhinitis: A protocol for systematic review and meta analysis.

BACKGROUND: Allergic rhinitis (AR) is a non-infectious chronic nasal mucosal disease mediated mainly by IgE, which affects 40% of the global population and has a recurrence rate of more than 50%. The modified Yupingfeng formula (MYPFF) is widely used in the treatment of allergic rhinitis in China. However, there is no evidence-based medical evidence for the efficacy and safety of MYPFF in the treatment of allergic rhinitis. METHODS: Database as China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), Wan-Fang Database, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and Web of Science will be searched for relevant literature from inception to September 2020. Data extraction will be performed on the obtained literature. Then RevMan V.5.3 will be used for the assessment of the risk of bias and data synthesis. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: The conclusion of the study will provide an evidence to efficacy and safety of MYPFF in treating allergic rhinitis, which will be of significant meaning for further research and clinical practice. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/RV9P4.

Safety of dietary supplements use among patients with cancer: A systematic review.

Dietary supplements (DS) are commonly taken by patients with cancer, but safety of DS use remains unclear. A systematic literature search was conducted using PubMed, ClinicalTrials.gov, International Pharmaceutical Abstracts and Alt HealthWatch databases from inception through October 12, 2018. Included studies were limited to clinical trials including patients with cancer, DS products as interventions, evaluation of safety endpoints of DS use, and published in English. Sixty-five studies were included to evaluate 20 different DS among patients with 12 types of cancer. Botanical DS (n = 13), vitamins (n = 8), and probiotics/synbiotics (n = 7) were the top 3 types of DS evaluated in these trials. Majority of studied DS appeared safe. Among 19 trials including patients with cancer undergoing chemotherapy, most (n = 18) of studied DS (e.g., vitamins, botanical, omega-3 fatty acid) were found to be safe. Evaluation of DS use and its safety should be regularly incorporated in clinical trials among patients with cancer.