Icariin improves learning and memory function in Aß1-42-induced AD mice through regulation of the BDNF-TrκB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim. is a traditional medicinal Chinese herb that is enriched with flavonoids, which have remarkably high medicinal value. Icariin (ICA) is a marker compound isolated from the total flavonoids of Epimedium brevicornu Maxim. It has been shown to improve Neurodegenerative disease, therefore, ICA is probably a potential drug for treating AD. MATERIALS AND METHODS: The 6-8-week-old SPF-class male ICR mice were randomly divided into 8 groups for modeling, and then the mice were administered orally with ICA for 21 days. The behavioral experiments were conducted to evaluate if learning and memory behavior were absent in mice, confirming that infusion of Amyloid ß-protein (Aß)1-42 caused significant memory impairment. The morphological changes and damage of neurons in the mice's brains were observed by HE and Nissl staining. The spinous protrusions (dendritic spines) on neuronal dendrites were investigated by Golgi-Cox staining. The molecular mechanism of ICA was examined by Western Blot. The protein docking of ICA and Donepezil with BDNF were analyzed to determine their interaction. RESULTS: The behavioral experimental results showed that in Aß1-42-induced AD mice, the learning and memory abilities were improved after using ICA. At the same time, the low, medium, and high doses of ICA could reduce the content of Aß1-42 in the hippocampus of AD mice, repair neuronal damage, enhance synaptic plasticity, as well as increase the expression of BDNF, TrκB, CREB, Akt, GAP43, PSD95, and SYN proteins in the hippocampus of mice. However, the effect with high doses of ICA is more pronounced. The high-dose administration of ICA has the best therapeutic effect on AD mice. After administering the inhibitor k252a, the therapeutic effect of ICA was reversed. The macromolecular docking results of ICA and BDNF protein demonstrated a strong interaction of -7.8 kcal/mol, which indicates that ICA plays a therapeutic role in AD mice by regulating the BDNF-TrκB signaling pathway. CONCLUSIONS: The results confirm that ICA can repair neuronal damage, enhance synaptic plasticity, as well as ultimately improve learning and memory impairment through the regulation of the BDNF-TrκB signaling pathway.

Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury.

Background: Hyperoxaluria is a major cause of oxalate nephropathy, which can lead to impaired renal function presenting as acute kidney injury, acute on chronic kidney disease, or chronic kidney disease. The Chronic Renal Insufficiency Cohort study showed that higher urinary oxalate is associated with renal outcome in patients with chronic kidney disease, supporting the nephrotoxicity of oxalate. Therefore, a better understanding of the role of oxalate in kidney injury is needed. This review describes the metabolism of oxalate and the clinical and pathology presentation of oxalate nephropathy. It also summarizes the available evidence for the underlying pathogenic mechanism and the development of treatments for oxalate-induced kidney injury. Summary: Disruption to any key step in the oxalate pathway including abnormal endogenous generation, ingestion of abnormally high dose of oxalate, increased absorption or attenuation of oxalate degradation in the gut, and reduced excretion through the kidney may lead to disrupted oxalate homeostasis. Oxalate nephropathy is mainly caused by hyperoxaluria. Oxalate crystal deposition in the kidney is usually accompanied with tubular toxicity, obstruction, interstitial fibrosis, and tubular atrophy. The mechanism of oxalate-induced renal injury has not been fully clarified. Evidence from both in vivo and in vitro studies shows that NLRP3 inflammasome activation and macrophage infiltration are involved in the processes of crystal adhesion, aggregation, and elimination and promote intrarenal inflammation and renal fibrosis. Novel treatment strategies have been developed and targeted therapies tested for oxalate nephropathy. Key Messages: Prompt diagnosis and management may help to reduce the deposition of calcium oxalate crystals in the kidney. Further studies are needed to clarify the underlying mechanisms to help develop more targeted therapies for oxalate nephropathy.

Bloodletting cupping combined with conventional measures therapy for psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Background: Psoriasis is an immune-mediated inflammatory disease prone to recurrence. Some studies indicated that bloodletting cupping combined with conventional measures therapy had been proposed as a treatment strategy for psoriasis. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness of this combination therapy in reducing the severity of disease in patients with psoriasis. Methods: The following electronic databases were searched for articles from January 1, 2000 to March 1, 2022: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), Wan-Fang Database, and China National Knowledge Infrastructure (CNKI). The language was not restricted while performing the search. The quality of articles was evaluated using Rev. Man 5.4 software (provided by the Cochrane Collaboration), comparing bloodletting cupping combined with conventional measures therapy to conventional measures treatments. The studies obtained randomized controlled trials (RCTs) of bloodletting cupping combined with conventional standard treatment for treating psoriasis. Two trained researchers (Xiaoyu Ma and Jiaming He) independently reviewed the literature, extracted data based on exclusion and inclusion criteria, and assessed the quality of the included studies. We estimated the aggregate data using a random effects model. Findings: We identified 164 studies. Ten studies met the inclusion criteria for the meta-analysis. The primary outcome indicator was the total number of effective individuals. Secondary outcomes included the Psoriasis Area and Severity Index (PASI), adverse effects, and the Dermatology Life Quality Index (DLQI). Compared with conventional treatments, bloodletting cupping combined with conventional medicine yielded an improved total effective number of persons (RR = 1.15, 95%CI: 1.07 to 1.22, p < 0.00001), PASI (MD = -1.11, 95%CI: -1.40 to -0.82, p < 0.00001) and DLQI scores (MD = -0.99, 95%CI: -1.40 to -0.59, p < 0.0001). We found no significant difference in adverse reactions (RR = 0.93, 95%CI: 0.46 to 1.90, p = 0.85). The heterogeneity test showed the total effective numbers (p < 0.00001, I 2 = 43%) and PASI (p < 0.00001, I 2 = 44%) and DLQI scores (p < 0.00001, I 2 = 0%). Interpretation: Bloodletting cupping combined with conventional treatment can achieve the ideal treatment for psoriasis. However, the combined treatment in psoriasis needs to be further evaluated in high-quality RCTs with large sample sizes to enable future studies in clinical use.

Protocatechuic Acid Delays Postovulatory Oocyte Ageing in Mouse.

SCOPE: Tea is a popular beverage worldwide and has many health functions. Protocatechuic acid (PCA) is an important bioactive component of tea and has benefit to health. In some cases, oocytes after ovulation may miss the optimal fertilization time and enter a postovulatory ageing process. Therefore, to investigate the role of PCA in delaying oocyte ageing is aimed. METHODS AND RESULTS: Metaphase II (MII) oocytes aged in vitro are randomly divided into three groups: control, aged, and aged + PCA. PCA treatment (30 µM) reduces the fragmentation rate and the incidence of abnormal spindle morphology and chromosome misalignment of oocytes aged 24 h in vitro. The mitochondrial dysfunction of aged oocytes, such as decreased mitochondrial membrane potential and excessive accumulation of reactive oxygen (ROS), is also alleviated by PCA. PCA also delays apoptosis of aged oocytes, and improves the sperm binding capacity. Otherwise, aged oocytes treated with PCA have a higher fertilization rate and blastocyst rate compared with untreated aged oocytes in vitro. CONCLUSION: PCA is an important bioactive ingredient of tea that improves aged oocyte quality, suggesting that PCA is available to improve the quality of aged oocytes in vitro.

Sustained release of Lactobacillus casei cell wall extract can induce a continuous and stable IgA deposition model.

Mucosal immune regulation is considered a key aspect of immunopathogenesis of IgA nephropathy (IgAN). Direct experimental evidence clarifying the role of intestinal mucosa attributes in IgAN is lacking. In this study, a mouse model was established via multiple low-dose intraperitoneal injections of Lactobacillus casei cell wall extract (LCWE) emulsified with Complete Freund's Adjuvant (CFA). We found continuous and stable deposition of IgA in glomerular mesangial areas, accompanying high circulating levels of IgA and IgA-IgG complexes. Expression of the key extracellular matrix components collagen IV and fibronectin also increased in the mesangial areas of LCWE-induced mice. IgA+ B220+ B-cell proportion increased in the small intestine (SI), Peyer's patches, inguinal lymph nodes, spleen, and bone marrow. The intestinal barrier was dysfunctional in the LCWE-induced mice, and consistent with this, higher levels of serum zonulin (namely prehaptoglobin-2), a regulator of epithelial and endothelial barrier function, were observed in patients with IgAN. Hematoxylin and eosin staining results indicated that immune tissues such as liver, spleen, and lymph nodes showed an inflammatory response and focal lesions. Glucocorticoid methylprednisolone treatment could alleviate serum IgA and IgA-IgG complex levels and mesangial IgA deposition. Taken together, our results indicate that we have successfully constructed a mouse model with IgA deposition in the mesangial areas of the glomeruli and provide evidence for the connection between the intestinal barrier and elevated circulating IgA and IgA-IgG in IgAN. © 2022 The Pathological Society of Great Britain and Ireland.

Integrated Bioinformatics Analysis for the Screening of Associated Pathways and Therapeutic Drugs in Coronavirus Disease 2019.

BACKGROUND: COVID-19 caused by a novel coronavirus, a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has recently broken out worldwide. Up to now, the development of vaccine is still in the stage of clinical research, and there is no clinically approved specific antiviral drug for human coronavirus infection. The purpose of this study is to investigate the key molecules involved in response during SARS-CoV-2 infection and provide references for the treatment of SARS-CoV-2. METHODS: We conducted in-depth and comprehensive bioinformatics analysis of human proteins identified with SARS-CoV-2, including functional enrichment analysis, protein interaction network analysis, screening of hub genes, and evaluation of their potential as therapeutic targets. In addition, we used the gene-drug database to search for inhibitors of related biological targets. RESULTS: Several significant pathways, such as PKA, centrosome and transcriptional regulation, may greatly contribute to the development and progression of COVID-2019 disease. Taken together 15 drugs and 18 herb ingredients were screened as potential drugs for viral treatment. Specially, the trans-resveratrol can significantly reduce the expression of N protein of MERS-CoV and inhibit MERS-CoV. In addition, trans-resveratrol, Epigallocatechin-3-gallate (EGCG) and BX795 all show good anti multiple virus effects. CONCLUSION: Some drugs selected through our methods have been proven to have antiviral effects in previous studies. We aim to use global bioinformatics analysis to provide insights to assist in the design of new drugs and provide new choices for clinical treatment.

Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis through miR-497-5p/AKT3 axis.

BACKGROUND: The roots of Salvia miltiorrhiza are used in traditional Chinese medicine (TCM) and have high medicinal value. Tanshinone IIA (Tan IIA) is the active ingredient of Salvia miltiorrhiza which can inhibit the growth of acute leukemia cell lines in vitro, although the mechanism remains unclear. METHODS: CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability. Western blot analysis was used to detect protein expression. miR-497-5p expression level was detected by using qRT-PCR, and Annexin V-FITC/propidium iodide (PI) was used to detect cell apoptosis. RESULTS: Here we reported that Tan IIA could inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis in acute myeloid leukemia (AML) cells. Thus, Tan IIA had the anti-cancer activity in AML cell lines, which was likely mediated by up-regulation of miR-497-5p expression. Our data further showed that in AML cells, the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic. We demonstrated that Tan IIA could inhibit the expression of AKT3 by up-regulating the expression of miR-497-5p. We subsequently identified that AKT3 was the direct target of miR-497-5p, and that treatment with Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions. In turn, PCNA expression was increased and cleaved Caspase-3 was suppressed, which contributed to the growth of AML cells. CONCLUSIONS: Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated AKT3 downregulation pathway.

The effectiveness of aromatherapy and massage on stress management in nurses: A systematic review.

AIMS AND OBJECTIVES: To assess the effectiveness of aromatherapy and massage on relieving stress in nurses. BACKGROUND: Nurses face uncommon levels of stress in medical settings. Stress has a negative impact on nurses' well-being and the organisation where they work. Aromatherapy and massage are important strategies for stress reduction. However, the effectiveness of aromatherapy and massage on relieving stress in nurses currently lacks understanding. DESIGN: Systematic review. METHOD: We performed a quantitative systematic review using Cochrane methods. We searched existing literature in the following databases: PubMed, PsycINFO, Embase, Web of Science and Cochrane Library, to examine any experimental design studies published from the earliest date available to August 2017 in English. Risk of bias per outcome was assessed. RESULTS: A total of 10 articles met the inclusion criteria, including aromatherapy (n = 4), massage (n = 4) and aromatherapy massage (n = 2). Most studies reported that aromatherapy and massage exert a beneficial effect on the stress of nurses. One study showed that the aromatherapy massage with music interventions has no effect on the stress of nurses. However, the number of the studies is limited and has high or unclear risk of bias. CONCLUSION: This review revealed that the evidence does not sufficiently prove that aromatherapy, massage and aromatherapy massage are effective for reducing job-related stress of nurses. We need to conduct high-quality studies to verify the effects of these interventions on nurses' stress levels in the future. Moreover, we need to integrate outcome measures of stress levels for developing more appropriate tools than the ones used as present. RELEVANCE TO CLINICAL PRACTICE: Nurses' stress has a negative impact on their own and organisation where they work. All available opportunities should be taken to reduce nurses' stress. It will be beneficial for nurse shortage.

Mineral and Bone Disorder and Its Association with Cardiovascular Parameters in Chinese Patients with Chronic Kidney Disease.

BACKGROUND: Mineral and bone disorder (MBD), especially hyperphosphatemia, is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD). However, CKD-MBD among Chinese population was poorly studied. This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD. METHODS: Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China. Markers of MBD, including serum phosphorus, calcium, and intact parathyroid hormone, were measured in baseline samples at the patients' entry. The association between serum phosphorus and abdominal aortic calcification (AAC), left ventricular hypertrophy (LVH) were examined by logistic regression models. RESULTS: Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml.min-1.1.73 m-2 were included. The proportion of patients with hyperphosphatemia were 2.6%, 2.9%, 6.8%, and 27.1% in CKD Stages 3a, 3b, 4, and 5, respectively. Moreover, 71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB). Lateral abdominal X-rays were obtained in 2280 patients, 9.8% of the patients were diagnosed as having AAC. Altogether 2219 patients had data of echocardiography, and 13.2% of them were diagnosed with LVH. Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH. CONCLUSIONS: In Chinese patients with CKD, the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal. The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.

[Short effect and adverse reaction of dog days plaster for allergic rhinitis].

OBJECTIVE: To evaluate the short effect and safety of the acupoint application of dog days for allergic rhinitis. METHODS: Two hundred and forty-nine patients were randomly divided into an application group (166 cases) and a placebo group (83 cases). On the first day of the first dog days, the first day of the second of the three ten-day periods of the hot season and the first day of the last of the three ten-day periods of the hot season, acupoint application was adopted mainly at Dazhui (GV 14), Feishu (BL 13), Pishu (BL 20) and Shenshu (BL 23) in the application group. The plaster was made of Chinese herbs, including Baijiezi (semen brassicae), Xixin (asarum), Yanhusuo (corydalis tuber) and Gansui (euphorbia kansui). Buckwheat plaster without medical ingredient was used in the placebo group. The application was pasted for 2-6 h every time. On the first three days of all the three periods of dog days, treatment was used continuously. The whole period of dog days was made into one course. The changes of symptom and syndrome scores, visual analogue scale (VAS) for symptom before and after treatment and the adverse reaction with the condition disposed were observed in the two groups. RESULTS: After treatment, the symptom and syndrome scores and VAS for symptom were improved compared with those before treatment in the two groups (all P < 0.05), and the improvements of the application group were more obvious than those of the placebo group (all P < 0.05). The short effective rate of the application group was 68.1% (113/166), which was better than 48.2% (40/83) of the placebo group (P < 0.05). The adverse reaction rates were 4.2% (7/166), 2.4% (2/83) respectively, with no statistical significance between the two groups (P > 0.05). CONCLUSION: The dog days plaster achieves obvious effect with good safety for allergic rhinitis.

Flavonoids in Juglans regia L. leaves and evaluation of in vitro antioxidant activity via intracellular and chemical methods.

Flavonoids are rich in Juglans regia L. leaves. They have potent antioxidant properties, which have been related to regulating immune function and enhancing anticancer activity. Herein, qualitative and quantitative determination of flavonoids from J. regia leaves was carried out using high performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionization and negative ion detection (HPLC-ESI-MS/MS) by comparison of the retention times and mass spectral fragments with standard substances or related literatures. Seventeen compounds were identified and major components are quercetin-3-O-rhamnoside (453.11 µg/g, dry weight), quercetin-3-O-arabinoside (73.91 µg/g), quercetin-3-O-xyloside (70.04 µg/g), kaempferol-O-pentoside derivative (49.04 µg/g), quercetin-3-O-galactoside (48.61 µg/g), and kaempferol-O-pentoside (48.46 µg/g). The in vitro intracellular antioxidation indicated that flavonoids from J. regia leaves could reduce the reactive oxygen species (ROS) level in RAW264.7 cells and showed good radical scavenging activities. These results proved to be more related to the flavonoids that could be considered in the design of new formulations of dietary supplements or functional foods.

Analysis by RP-HPLC of mangiferin component correlation between medicinal loranthus and their mango host trees.

This study proposes a reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of mangiferin in medicinal loranthus shrubs and their mango or non-mango host trees. Mangiferin in samples was extracted with a solution of 40% methanol. Analytical determination was conducted by RP-HPLC with ultraviolet detection at 258 nm. Chromatographic separation was achieved on an Inertsil ODS-SP column (250 × 4.6 mm, 5 µm) by isocratic elution with methanol-0.1% aqueous phosphoric acid (31:69, v/v). Mangiferin contents were 5.04 to 18.95 mg/g in mango trees and 0.44 to 3.72 mg/g in medicinal loranthus parasitized on mango host trees. Mangiferin could not be detected in non-mango trees and their loranthus shrubs. This study indicated that host trees could affect the quality of medicinal loranthus by transporting host-inherent components into loranthus.

[Correlation of DNJ between taxilli herba and its host-plants].

OBJECTIVE: To study the correlation of 1-deoxynojirimycin (DNJ) between Taxilli Herba parasitized in mulberry and its host-plants. METHOD: The contents of DNJ of Taxilli Herba parasitized in mulberry and non-mulberry were determined by RP-HPLC. DNJ was extracted with 0.05 mol x L(-1) HCl, and then detected by fluorescence detector after derivatized with FMOC-Cl at pH 8.0 with borate buffer. The separation was performed on an Agilent C18 (4.6 mm x 250 mm, 5 microm) column with a mobile phase of acetonitrile-0.1% aqueous acetic acid (51: 49) at a flow rate of 1.0 mL x min(-1). The wavelength of fluorescence detector was operated at lambda(EX) = 254 nm and lambda(EM) = 322 nm. RESULT: The linear range of DNJ was 3.72-37.2 mg x L(-1) (r = 0.999 9). The average recovery was 96.42%. The contents of DNJ in mulberry and Taxilli Herba parasitized in mulberry were 1.39-10.16 mg x g(-1) and 0.46-2.72 mg x g(-1), respectively. However, the contents of DNJ could not be detected in Taxilli Herba parasitized in non mulberry and its host-plants. CONCLUSION: As the characteristic constituent of mulberry, DNJ was accumulated in Taxilli Herba This method can be applied to the quality control of Taxilli Herba from mulberry.