Glycated Walnut Meal Peptide-Calcium Chelates: Preparation, Characterization, and Stability.

Finding stable and bioavailable calcium supplements is crucial for addressing calcium deficiency. In this study, glycated peptide-calcium chelates (WMPHs-COS-Ca) were prepared from walnut meal protein hydrolysates (WMPHs) and chitosan oligosaccharides (COSs) through the Maillard reaction, and the structural properties and stability of the WMPHs-COS-Ca were characterized. The results showed that WMPHs and COSs exhibited high binding affinities, with a glycation degree of 64.82%. After glycation, Asp, Lys, and Arg decreased by 2.07%, 0.46%, and 1.06%, respectively, which indicated that these three amino acids are involved in the Maillard reaction. In addition, compared with the WMPHs, the emulsifying ability and emulsion stability of the WMPHs-COS increased by 10.16 mg2/g and 52.73 min, respectively, suggesting that WMPHs-COS have better processing characteristics. After chelation with calcium ions, the calcium chelation rate of peptides with molecular weights less than 1 kDa was the highest (64.88%), and the optimized preparation conditions were 5:1 w/w for WMPH-COS/CaCl2s, with a temperature of 50 °C, a chelation time of 50 min, and a pH of 7.0. Scanning electron microscopy showed that the "bridging role" of WMPHs-COS changed to a loose structure. UV-vis spectroscopy and Fourier transform infrared spectrometry results indicated that the amino nitrogen atoms, carboxyl oxygen atoms, and carbon oxygen atoms in WMPHs-COS chelated with calcium ions, forming WMPHs-COS-Ca. Moreover, WMPHs-COS-Ca was relatively stable at high temperatures and under acidic and alkaline environmental and digestion conditions in the gastrointestinal tract, indicating that WMPHs-COS-Ca have a greater degree of bioavailability.

Nitrogen-phosphorus dual-doped auricularia auricula porous carbon as host for Li-S battery.

A nitrogen-phosphorus dual-doped porous spore carbon (NP-PSC) positive electrode matrix was prepared using native auricularia auricula as solid medium based on the principle of biomass rot. Yeast was introduce and cultured by the auricularia auricula solid medium. The freeze-drying and carbonization activation processes made the materials present a three-dimensional porous spore carbon aerogel properties. Yeast fermentation transformed auricularia auricula from blocky structure to porous structure and introduced nitrogen-phosphorus dual-doping. The physical and chemical properties of the prepared materials were characterized in detail. Electrochemical performance of NP-PSC in Li-S batteries was systematically investigated. Porous structure and heteroatom-doping improved the electrochemical performance, which is much superior to conventional activated carbon materials.

Impact of Chinese herbal medicine on sarcopenia in enhancing muscle mass, strength, and function: A systematic review and meta-analysis of randomized controlled trials.

Sarcopenia has become important to the public health with the increase in the aging population in society. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise, and nutritional intervention, are far from satisfactory. Chinese herbal medicine is a new treatment format with interesting possibilities in sarcopenia has been widely practiced. The study aims to explore the effectiveness of Chinese herbal medicine in sarcopenia. We comprehensively searched the following electronic databases: Medline, EMBASE, APA PsycInfo, Cochrane Library, Web of Science, PubMed, and Chinese database from the establishment of the database to December 2022 (no language restrictions). Randomized controlled clinical studies on the use of Chinese herbal medicine in sarcopenia were selected in compliance with PRISMA guidelines. Review Manager and Stata were used for statistical analysis and the mean difference and standardized mean difference were adopted. Of 277 identified studies, 17 were eligible and included in our analysis (N = 1440 participants). The results showed that Chinese herbal medicine can improve total efficiency (RR = 1.29, 95% CI [1.21, 1.36], p < 0.00001) in sarcopenia and enhance muscle mass (SMD = 1.02, 95% CI [0.55, 1.50], p < 0.0001), and muscle strength measured by grip strength (SMD = 0.66, 95% CI [0.36, 0.96], p < 0.0001), measured by 60°/s knee extension peak TQ (MD = 5.63, 95% CI [-0.30, 11.57], p = 0.06) and muscle function measured by 6-meter walking speed (SMD = 1.34, 95% CI [0.60, 2.08], p = 0.0004), measured by the short physical performance battery of 1.50%, 95% CI (1.05, 1.95), measured by the EuroQoL 5-dimension of (SMD = 0.27, 95% CI [-0.10, 0.65], p = 0.16), suggesting that Chinese herbal medicine alone or combined with conventional treatment has ameliorating effect on sarcopenia. Chinese herbal medicine is a potential therapeutic strategy in sarcopenia. The funnel plot and Egger's test indicated publication bias. To confirm our conclusions, further high-quality studies should be conducted.

Peony Pollen Protects against Primary Dysmenorrhea in Mice by Inhibiting Inflammatory Response and Regulating the COX2/PGE2 Pathway.

Peony pollen contains multiple nutrients and components and has been used as a traditional Chinese medicine with a long history, but the effect of the treatment of primary dysmenorrhea remains to be clarified. The aim of this study is to investigate the therapeutic effect of peony pollen on primary dysmenorrhea mice and the potential mechanism. A uterus contraction model in vitro and primary dysmenorrhea mice were used to evaluate the treatment effect of peony pollen on primary dysmenorrhea. The primary dysmenorrhea mice were treated with 62.5 mg/kg, 125 mg/kg, or 250 mg/kg of peony pollen, and the writhing response, latency period, histopathological changes in the uterus, prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) levels, and infiltration of neutrophils and macrophages were investigated. Protein expression of interleukin 1 ß (IL-1ß), interleukin 6 (IL-6), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase 1 (mPGEs-1), BCL2-Associated X (Bax), B-cell lymphoma-2 (BCL-2), caspase-3, and cleaved caspase-3 were detected by Western blot, and the oxidative stress related marker malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were evaluated. Peony pollen could attenuate spontaneous or oxytocin-induced uterus contractions in vitro. Moreover, peony pollen decreased the writhing times, prolonged the writhing latency, and reduced the pathological damage of uterine tissues. Furthermore, the inflammatory cell infiltration and the protein expression of IL-1ß, IL-6, and NLRP3 were decreased. The COX-2/PGE2 pathway was inhibited; oxidative stress and apoptosis in the uterus also improved in the uterus of primary dysmenorrhea mice. Peony pollen exerts a positive effect on primary dysmenorrhea by inhibiting the inflammatory response and modulating oxidative stress and apoptosis by regulating the COX-2/PGE2 pathway.

Short-term dietary choline supplementation alters the gut microbiota and liver metabolism of finishing pigs.

Choline is an essential nutrient for pig development and plays a role in the animal's growth performance, carcass characteristics, and reproduction aspects in weaned pigs and sows. However, the effect of choline on finishing pigs and its potential regulatory mechanism remains unclear. Here, we feed finishing pigs with 1% of the hydrochloride salt of choline, such as choline chloride (CHC), under a basic diet condition for a short period of time (14 days). A 14-day supplementation of CHC significantly increased final weight and carcass weight while having no effect on carcass length, average backfat, or eye muscle area compared with control pigs. Mechanically, CHC resulted in a significant alteration of gut microbiota composition in finishing pigs and a remarkably increased relative abundance of bacteria contributing to growth performance and health, including Prevotella, Ruminococcaceae, and Eubacterium. In addition, untargeted metabolomics analysis identified 84 differently abundant metabolites in the liver between CHC pigs and control pigs, of which most metabolites were mainly enriched in signaling pathways related to the improvement of growth, development, and health. Notably, there was no significant difference in the ability of oxidative stress resistance between the two groups, although increased bacteria and metabolites keeping balance in reactive oxygen species showed in finishing pigs after CHC supplementation. Taken together, our results suggest that a short-term supplementation of CHC contributes to increased body weight gain and carcass weight of finishing pigs, which may be involved in the regulation of gut microbiota and alterations of liver metabolism, providing new insights into the potential of choline-mediated gut microbiota/metabolites in improving growth performance, carcass characteristics, and health.

The effect of vitamin D supplementation on some metabolic parameters in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 8 RCTs.

BACKGROUND: To systematically evaluate the effects of vitamin D supplementation in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science, WANFANG databases, and Google Scholar were retrieved to collect relevant randomized controlled trials, which are published from the earliest records the time the database was created to April 2023. Meta-analysis was conducted by using Review Manager 5.4 software after evaluating in terms of inclusion and exclusion criteria. The outcome indicators include 25-hydroxyvitamin D [25(OH)D] levels, insulin resistance index (homeostasis model assessment of insulin resistance), fasting blood glucose, and fasting insulin levels (FINS). RESULTS: Eight randomized controlled trials with a total of 657 patients are included. Vitamin D supplementation increased 25(OH)D levels significantly (mean difference [MD] = 2.01, 95% confidence intervals [CI]: 0.94 to 3.08, P < .05) and vitamin D supplementation had a significant effect on insulin resistance index (MD = -0.54, 95% CI: -1.28 to 0.20, P = .16), fasting glucose (MD = -0.59, 95% CI: -1.50 to 0.32, P = .20), and FINS levels (MD = -0.30, 95% CI: -0.77 to 0.17, P = .21) had no significant effect. CONCLUSION: Vitamin D supplementation improves 25(OH)D levels in patients with nonalcoholic fatty liver disease, but there is no effect on homeostasis model assessment of insulin resistance, fasting blood glucose, or FINS.

Oxytetracycline-induced oxidative liver damage by disturbed mitochondrial dynamics and impaired enzyme antioxidants in largemouth bass (Micropterus salmoides).

Oxytetracycline (OTC), a commonly used tetracycline antibiotic in aquaculture, has been found to cause significant damage to the liver of largemouth bass (Micropterus salmoides). This study revealed that OTC can lead to severe histopathological damage, structural changes at the cellular level, and increased levels of reactive oxygen species (ROS) in M. salmoides. Meanwhile, OTC impairs the activities of antioxidant enzyme (such as T-SOD, CAT, GST, GR) by suppressing the activation of MAPK/Nrf2 pathway. OTC disrupts mitochondrial dynamics and mitophagy through via PINK1/Parkin pathway. The accumulation of damaged mitochondria, combined with the inhibition of the antioxidant enzyme system, contributes to elevated ROS levels and oxidative liver damage in M. salmoides. Further investigations demonstrated that an enzyme-treated soy protein (ETSP) dietary supplement can help maintain mitochondrial dynamic balance by inhibiting the PINK1/Parkin pathway and activate the MAPK/Nrf2 pathway to counteract oxidative damage. In summary, these findings highlight that exposure to OTC disrupts mitochondrial dynamics and inhibits the antioxidant enzyme system, ultimately exacerbating oxidative liver damage in M. salmoides. We propose the use of a dietary supplement as a preventive measure against OTC-related side effects, providing valuable insights into the mechanisms of antibiotic toxicity in aquatic environments.

Efficacy and safety of Tuina (Chinese Therapeutic Massage) for knee osteoarthritis: A randomized, controlled, and crossover design clinical trial.

Background: Knee osteoarthritis (KOA) is a highly prevalent joint disease among the middle-aged and elderly population that can lead to pain, functional impairment, decreased quality of life, and a large number of medical expenses. Physical therapy is one of the main treatment methods for KOA. In China, Tuina has been widely used in the treatment of KOA, but up to now, there is no high-quality medical evidence to support its effectiveness and safety. The purpose of this study was to objectively evaluate the efficacy and safety of Tuina in the treatment of KOA. Methods: A crossover design clinical trial was performed on 96 patients. The test group and the control group in the trial were allocated randomly in a ratio of 1:1. The test group received Tuina treatment for 4 weeks first and then received health education intervention for another 4 weeks. The control group received health education intervention for 4 weeks first and then received Tuina treatment for another 4 weeks. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score was chosen as the primary outcome. The WOMAC pain score, WOMAC stiffness, WOMAC daily activity score, and visual analog scale (VAS) score were the secondary outcomes. Adverse events during the intervention were collected in both groups. Results: Compared with the baseline, the WOMAC total score, WOMAC pain score, WOMAC stiffness, WOMAC daily activity, and VAS score of patients in both groups were improved significantly at weeks 4 and 8 (p < 0.001). All patients who received Tuina treatment were significantly superior to those who received health education intervention in the WOMAC total score (194.96, 95% CI = 164.94-224.97, P < 0.001), WOMAC pain score (45.96, 95% CI = 35.82-56.09, P < 0.001), WOMAC stiffness (31.42, 95% CI = 26.37-36.46, P < 0.001), WOMAC daily activity (117.58, 95% CI = 97.56-137.61, P < 0.001), and VAS score (1.07, 95% CI = 0.83-1.32, P < 0.001). Both groups had no serious adverse events during the treatment. Conclusion: This trial demonstrated that Tuina can reduce joint pain in patients with KOA and improve the physical functions of the knee joint effectively and safely. Clinical trial registration: This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR-TTRCC-13003157). http://www.chictr.org.cn/showproj.aspx?proj=6402.

Dietary Leucine Improves Fish Intestinal Barrier Function by Increasing Humoral Immunity, Antioxidant Capacity, and Tight Junction.

This study attempted to evaluate the possible impact and mechanism of leucine (Leu) on fish intestinal barrier function. One hundred and five hybrid Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂ catfish were fed with six diets in graded levels of Leu 10.0 (control group), 15.0, 20.0, 25.0, 30.0, 35.0, and 40.0 g/kg diet for 56 days. Results showed that the intestinal activities of LZM, ACP, and AKP and contents of C3, C4, and IgM had positive linear and/or quadratic responses to dietary Leu levels. The mRNA expressions of itnl1, itnl2, c-LZM, g-LZM, and ß-defensin increased linearly and/or quadratically (p < 0.05). The ROS, PC, and MDA contents had a negative linear and/or quadratic response, but GSH content and ASA, AHR, T-SOD, and GR activities had positive quadratic responses to dietary Leu levels (p < 0.05). No significant differences on the CAT and GPX activities were detected among treatments (p > 0.05). Increasing dietary Leu level linearly and/or quadratically increased the mRNA expressions of CuZnSOD, CAT, and GPX1α. The GST mRNA expression decreased linearly while the GCLC and Nrf2 mRNA expressions were not significantly affected by different dietary Leu levels. The Nrf2 protein level quadratically increased, whereas the Keap1 mRNA expression and protein level decreased quadratically (p < 0.05). The translational levels of ZO-1 and occludin increased linearly. No significant differences were indicated in Claudin-2 mRNA expression and protein level. The transcriptional levels of Beclin1, ULK1b, ATG5, ATG7, ATG9a, ATG4b, LC3b, and P62 and translational levels of ULK1, LC3Ⅱ/Ⅰ, and P62 linearly and quadratically decreased. The Beclin1 protein level was quadratically decreased with increasing dietary Leu levels. These results suggested that dietary Leu could improve fish intestinal barrier function by increasing humoral immunity, antioxidative capacities, and tight junction protein levels.

Guanxining injection alleviates fibrosis in heart failure mice and regulates SLC7A11/GPX4 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort., Apiaceae, Chuanxiong in Chinese) both are important traditional Chinese medicine (TCM) for activating blood and eliminating stasis. Danshen-chuanxiong herb pair has been used for more than 600 years in China. Guanxinning injection (GXN) is a Chinese clinical prescription refined from aqueous extract of Danshen and Chuanxiong at the ratio of 1:1 (w/w). GXN has been mainly used in the clinical therapy of angina, heart failure (HF) and chronic kidney disease in China for almost twenty years. AIM OF THE STUDY: This study aimed to explore the role of GXN on renal fibrosis in heart failure mice and the regulation of GXN on SLC7A11/GPX4 axis. MATARIALS AND METHODS: The transverse aortic constriction model was used to mimic HF accompanied by kidney fibrosis model. GXN was administrated by tail vein injection in dose of 12.0, 6.0, 3.0 mL/kg, respectively. Telmisartan (6.1 mg/kg, gavage) was used as a positive control drug. Cardiac ultrasound indexes of ejection fraction (EF), cardiac output (CO), left ventricle volume (LV Vol), HF biomarker of pro-B type natriuretic peptide (Pro-BNP), kidney function index of serum creatinine (Scr), kidney fibrosis index of collagen volume fraction (CVF) and connective tissue growth factor (CTGF) were evaluated and contrasted. Metabolomic method was employed to analyze the endogenous metabolites changes in kidneys. Besides, contents of catalase (CAT), xanthine oxidase (XOD), nitricoxidesynthase (NOS), glutathione peroxidase 4 (GPX4), the x(c)(-) cysteine/glutamate antiporter (SLC7A11) and ferritin heavy chain (FTH1) in kidney were quantitatively analyzed. In addition, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical composition of GXN and network pharmacology was used to predict possible mechanisms and the active ingredients of GXN. RESULTS: The cardiac function indexes of EF, CO and LV Vol, kidney functional indicators of Scr, the degree of kidney fibrosis indicators CVF and CTGF were all relieved to different extent for the model mice treated with GXN. 21 differential metabolites involved in redox regulation, energy metabolism, organic acid metabolism, nucleotide metabolism, etc were identified. Aspartic acid, homocysteine, glycine, and serine, methionine, purine, phenylalanine and tyrosine metabolism were found to be the core redox metabolic pathways regulated by GXN. Furthermore, GXN were found to increase CAT content, upregulate GPX4, SLC7A11 and FTH1 expression in kidney significantly. Not only that, GXN also showed good effect in down-regulating XOD and NOS contents in kidney. Besides, 35 chemical constituents were initially identified in GXN. Active ingredients of GXN-targets-related enzymes/transporters-metabolites network was established to find out that GPX4 was a core protein for GXN and the top 10 active ingredients with the most relevant to renal protective effects of GXN were rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A. CONCLUSION: GXN could significantly maintain cardiac function and alleviate the progression of fibrosis in the kidney for HF mice, and the mechanisms of action were related to regulating redox metabolism of aspartate, glycine, serine, and cystine metabolism and SLC7A11/GPX4 axis in kidney. The cardio-renal protective effect of GXN may be attributed to multi-components like rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A et al.

Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis.

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1ß, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.

Pectic polysaccharides derived from Hainan Rauwolfia ameliorate NLR family pyrin domain-containing 3-mediated colonic epithelial cell pyroptosis in ulcerative colitis.

Pectic polysaccharides (PPs) could exert functions on ulcerative colitis (UC), which is classified as a nonspecific inflammatory disorder. This study investigated the molecular mechanism of PPs derived from Rauwolfia in UC. First, the dextran sodium sulfate (DSS)-induced mouse colitis models and lipopolysaccharide (LPS)-treated colonic epithelial cell (YAMC) models were established and treated with PP. Subsequently, the effects of PPs on mucosal damages in DSS mice were detected, and the levels of inflammatory cytokines, pyroptosis-related factors, oxidative stress-related markers, and the tight junction-related proteins in the tissues or cells were examined, and the results suggested that PPs ameliorated colonic mucosal damages and cell pyroptosis in DSS mice, and limited colonic epithelial cell pyroptosis in in vitro UC models. Subsequently, the binding relations of retinol-binding protein 4 (RBP4) to miR-124-3p and NLR pyrin domain-containing 3 (NLRP3) were analyzed. miR-124-3p targeted RBP4 and reduced the binding of RBP4 to NLRP3, thus inhibiting NLRP3-mediated pyroptosis. Finally, functional rescue experiments revealed that miR-124-3p suppression or RBP4 overexpression promoted colonic epithelial cell pyroptosis. Collectively, Rauwolfia-derived PPs limited miR-124-3p and targeted RBP4 and reduced the binding potency of RBP4 to NLRP3 to inhibit NLRP3-mediated pyroptosis, resulting in the alleviation of colonic epithelial cell pyroptosis and mucosal damages in UC.

Five New Diarylbutyrolactones and Sesquilignans from Saussurea medusa and Their Inhibitory Effects on LPS-induced NO Production.

Five new diarylbutyrolactones and sesquilignans (1A/1B:  - 4: ), including one pair of enantiomers (1A/1B: ), together with 10 known analogues (5:  - 14: ), were isolated from the whole plants of Saussurea medusa. Compound 1: was found to possess an unusual 7,8'-diarylbutyrolactone lignan structure. Separation by chiral HPLC analysis led to the isolation of one pair of enantiomers, (+)-1A: and (-)-1B: . The structures of the new compounds were elucidated by extensive spectroscopic data. All compounds, except compounds 5, 7: and 9: , were isolated from S. medusa for the first time. Moreover, compounds 1:  -  4, 8: and 10:  - 14: had never been obtained from the genus Saussurea previously. Compounds (+)- 1A, 2, 5, 7: , and 9:  - 11: were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC50 values ranging from 10.1 ± 1.8 to 41.7 ± 2.1 µM. Molecular docking and iNOS expression experiments were performed to examine the interactions between the active compounds and the iNOS enzyme.

Test reliability and comparability of paper and Chinese electronic version of the western Ontario and McMaster University osteoarthritis index: protocol for a randomised controlled clinical trial.

INTRODUCTION: The Western Ontario and McMaster University osteoarthritis index (WOMAC) is the most commonly used indicator of disease-specific outcome in knee osteoarthritis for its convenience and reliability. It has two formats the paper-based WOMAC (p-WOMAC) and the electronic WOMAC (e-WOMAC). In China, the p-WOMAC has been widely used though e-WOMAC is yet untested. This study aims to test whether e-WOMAC is consistent with the p-WOMAC before and after the intervention. METHODS AND ANALYSIS: A total of 70 patients from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine will be randomly assigned in two groups, named, group A and group B. This study is divided into three stages. In the first stage, patients in group A will be evaluated first by p-WOMAC and then by e-WOMAC. Patients in group B will be evaluated by e-WOMAC and then by p-WOMAC. In the second stage of the study, drug interventions will be implemented. 200 mg celecoxib will be administered orally once a day starting from the second day of enrolment for a period of 21 days. In the third stage, postintervention evaluation will be conducted after administration. Patients in group A will be evaluated first by e-WOMAC and then by p-WOMAC. Patients in group B will be evaluated first by p-WOMAC and then by e-WOMAC. In order to avoid the possible bias because of patients' potential memory, e-WOMAC and p-WOMAC will be taken for each patient at 15 min apart. The primary outcome of the study is the mean score difference in WOMAC, and the secondary outcomes are the score differences in WOMAC subscales: pain, stiffness and physical function. ETHICS AND DISSEMINATION: The protocol has been approved by the Independent Review Board of SGH (approval number: 2020-814-21-01). The results of the trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100050914.

Protective effects of black onion polysaccharide on liver and kidney injury in T2DM rats through the synergistic impact of hypolipidemic and antioxidant abilities.

In this study, the synergistic effects of black onion on the hypolipidemic and antioxidant activities in T2DM rats induced by a high-fat-diet and alloxan were investigated. The results showed that the fasting blood glucose of diabetic rats was significantly decreased after treatment with black onion polysaccharide (p < 0.01). Blood lipid analysis indicated that black onion polysaccharide could significantly improve the abnormal metabolism of blood lipids caused by diabetes. In addition, the MDA and ROS of the diabetic rats treated with black onion polysaccharide were significantly reduced; moreover, SOD was increased, indicating the excellent antioxidant activity of black onion polysaccharide. A histological examination clearly showed that black onion polysaccharide could improve the histological morphology of the liver and kidney. Furthermore, the indices of liver and kidney function were restored. These results indicate that black onion polysaccharide can reduce blood glucose and simultaneously show synergistic effects of hypoglycemic and antioxidant activities in diabetic rats. Therefore, black onion polysaccharide may alleviate liver and kidney function injury by improving the "two-hit" mechanism and can thus be used as a potential functional food to prevent diabetes and its complications.

Vitamin A in children's pneumonia for a COVID-19 perspective: A systematic review and meta-analysis of 15 trials.

BACKGROUND: To systematically review and meta-analyze the efficacy of vitamin A as an adjuvant therapy for pneumonia in children. METHODS: We searched in PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure, WanFang Database and Chongqing VIP information network from libraries building to March 2022, screening randomized controlled trials (RCT) about vitamin A combined with conventional therapy for pneumonia in children. Two researchers used the Cochrane risk of bias tool to assess the quality of included studies dependently. Data analysis was conducted in the RevMan 5.3. RESULTS: 15 trials involving 3496 patients (treated group: 1898; control group: 1598) were analyzed in this study. The Meta-analysis showed that vitamin A combined with conventional therapy improved clinical efficacy (P < .05), shortened the duration of fever and cough, negative time of chest X-ray, and the hospitalization, lung rale disappearance, choking milk disappearance, shortness of breath disappearance and perilabial cyanosis disappearance (P < .05). However, vitamin A combined with conventional therapy did not reduce the mortality of pneumonia in children (P > .05). CONCLUSION: Vitamin A contributes to relieve the clinical symptoms and signs, and also shorten the hospitalization.

Therapeutic potential of plant iridoids in depression: a review.

CONTEXT: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. OBJECTIVE: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. METHODS: The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression. RESULTS: Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. DISCUSSION AND CONCLUSIONS: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.

Cinobufagin induces acute promyelocytic leukaemia cell apoptosis and PML-RARA degradation in a caspase-dependent manner by inhibiting the ß-catenin signalling pathway.

CONTEXT: Acute promyelocytic leukaemia (APL) is a malignant hematological tumour characterized by the presence of promyelocytic leukaemia-retinoic acid receptor A (PML-RARA) fusion protein. Cinobufagin (CBG) is one of the main effective components of toad venom with antitumor properties. However, only a few reports regarding the CBG treatment of APL are available. OBJECTIVE: We explored the effect and mechanism of action of CBG on NB4 and NB4-R1 cells. MATERIALS AND METHODS: We evaluated the viability of NB4 and NB4-R1 cells treated with 0, 20, 40, and 60 nM CBG for 12, 24, and 48 h. After treatment with CBG for 24 h, Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl-2), ß-catenin, cyclin D1, and c-myc expression was detected using western blotting and real-time polymerase chain reaction. Caspase-3 and PML-RARA expression levels were detected using western blotting. RESULTS: CBG inhibited the viability of NB4 and NB4-R1 cells. The IC50 values of NB4 and NB4-R1 cells treated with CBG for 24 h were 45.2 nM and 37.9 nM, respectively. CBG induced NB4 and NB4-R1 cell apoptosis and PML-RARA degradation in a caspase-dependent manner and inhibited the ß-catenin signalling pathway. DISCUSSION AND CONCLUSION: CBG induced NB4 and NB4-R1 cell apoptosis and PML-RARA degradation in a caspase-dependent manner by inhibiting the ß-catenin signalling pathway. This study proposes a novel treatment strategy for patients with APL, particularly those with ATRA-resistant APL.

Treatment of sensitive skin by short-wave radiofrequency combined with intense pulsed light.

BACKGROUND: Sensitive skin is a widespread dermatologic condition, and no optimal treatments have been established so far. OBJECTIVE: To investigated the efficacy and safety of the combined therapy of short-wave radiofrequency (SWRF) and intense pulsed light (IPL) in improving transepidermal water loss (TEWL) and facial erythema in sensitive skin patients. METHODS: Twenty-two patients with sensitive skin received the SWRF treatment once per week for 4 weeks and IPL treatment once. Digital photographs and three-dimensional images were taken at each follow-up. The clinical efficacy was evaluated by the improvement of sensitive scale-10 including irritant symptoms and facial erythema. In addition, erythema area and TEWL values were measured. RESULTS: All patients showed subjective and objective improvement in irritant sensations and facial erythema after treatment. The TEWL values decreased from 20.29 ± 5.97 g·h-1 ·m-2 at baseline to 14.70 ± 6.02 g·h-1 ·m-2 after SWRF treatment and 13.78 ± 4.70 g·h-1 ·m-2 after combined therapy (p = 0.000). The clearance of the erythema area was statistically significant, with 14.05% ± 5.71% at baseline, 9.38% ± 4.08% after SWRF treatment, and 5.73% ± 2.79% after combined therapy (p = 0.000). No adverse events were observed. CONCLUSIONS: The combination of SWRF with IPL was effective in relieving skin irritant sensations and facial erythema of sensitive skin by repairing skin barrier function.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.