Correlation Between Persistent HPV Infection and Vaginal Microecological Imbalance After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Objective: To analyze the association between persistent human papillomavirus (HPV) infection and vaginal microecological imbalance after surgical treatment of cervical high-grade squamous intraepithelial lesion (HSIL). Methods: This is a retrospective study, 180 cervical HSIL patients admitted to our hospital from May 2019 to May 2021 were selected, of these, 84 were treated with loop electrosurgical excision procedure (LEEP) and 96 with cold knife conization (CKC). Patients were followed up for HPV infection 1 year after surgery. There is a division into a persistent infection group (positive group) and a negative group based on the presence or absence of HPV, the detection technique was PCR amplification. The two groups were compared regarding preoperative HPV infection, vaginal micro-ecological indicators 1 year after surgery, and the correlation between persistent HPV infection and vaginal microecological imbalance. Results: At 1 year after surgery, among 180 cervical HSIL patients, 64 (35.56%) were persistently infected with HPV, with an age of (40.20 ± 4.85) years, including 36 (56.25%) with cervical intraepithelial neoplasia (CIN) grade II, 28 (43.75%) with cervical intraepithelial neoplasia (CIN) grade III, 116 (64.44%) with HPV negative, with an age of (40.22 ± 5.15) years, including 67 (57.76%) with CIN grade II and 49 (42.24%) with CIN grade III, the differences in age and CIN classification between the two groups were not statistically significant (P > .05). Preoperatively, 53 people (82.81%) with HPV viral load >100 RLU/CO in the HPV persistent infection group and 76 people (65.52%) with HPV viral load >100 RLU/CO in the HPV negative group, with statistically significant differences between the two groups (P < .05); The difference in HPV virus typing and HPV infection type between the two groups was not statistically significant (P > .05). At 1 year after surgery, the composition ratio of flora density class IV and flora diversity class IV were significantly higher in the HPV persistent infection group than in the HPV negative group, and the dominant bacteria were mainly gram-positive large bacillus, accounting for 83.33%, the difference between the two groups was statistically significant (P < .05); The differences in Nugent scores and pH values between the two groups were not statistically significant (P > .05). Logistic regression analysis showed that flora density, flora diversity, and dominant bacteria were all independent risk factors for persistent HPV infection after treatment in patients with HSIL (P < .05). Conclusion: After treatment of HSIL patients, clinical attention should be paid to monitoring of HPV infection but also to the changes in vaginal microecology, as timely correction of vaginal microecology can facilitate HPV regression and improve the patient's prognosis.

An Interview Study of College Students' Health Emergency Literacy in the Context of COVID-19 Normalized Prevention and Control.

Objective: To explore the changes in college students' awareness of health protection under the normalization of COVID-19, and to seek its connection with the epidemic management in colleges and universities, so as to provide reference information for continuous health education activities and the cultivation of college students' health emergency literacy in colleges and universities. Methods: Qualitative interviews were used to understand the extent of health emergency literacy among college students enrolled in the context of a normalized epidemic and the factors associated with it that cause changes around a question outline. Results: The interviewees generally had a lax mentality in the late stage of the interview, the importance they attached to epidemic prevention and control decreased significantly, and the way to know about epidemic protection measures and other knowledge was mainly through the mass news media. All respondents affirm the importance of social software for outbreak prevention and control. All 17 interviewees were able to mention basic outbreak protection methods, but 15 of them showed inconsistent behavior in words and actions later. Conclusion: The vast majority of respondents' health emergency literacy appears to weaken in the late stages of epidemic normalization, and the effect of traditional approaches used by universities to improve college students' health emergency literacy is weak.

Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest.

Increasing evidence shows that SARS-CoV-2 can infect kidneys and cause acute kidney injury (AKI) in critically ill COVID-19 patients. However, mechanisms through which COVID-19 induces AKI are largely unknown, and treatment remains ineffective. Here, we report that kidney-specific overexpressing SARS-CoV-2 N gene can cause AKI, including tubular necrosis and elevated levels of serum creatinine and BUN in 8-week-old diabetic db/db mice, which become worse in those with older age (16 weeks) and underlying diabetic kidney disease (DKD). Treatment with quercetin, a purified product from traditional Chinese medicine (TCM) that shows effective treatment of COVID-19 patients, can significantly inhibit SARS-CoV-2 N protein-induced AKI in diabetic mice with or without underlying DKD. Mechanistically, quercetin can block the binding of SARS-CoV-2 N protein to Smad3, thereby inhibiting Smad3 signaling and Smad3-mediated cell death via the p16-dependent G1 cell-cycle arrest mechanism in vivo and in vitro. In conclusion, SARS-CoV-2 N protein is pathogenic and can cause severe AKI in diabetic mice, particularly in those with older age and pre-existing DKD, via the Smad3-dependent G1 cell-cycle arrest mechanism. Importantly, we identify that quercetin may be an effective TCM compound capable of inhibiting COVID-19 AKI by blocking SARS-CoV-2 N-Smad3-mediated cell death pathway.

Resveratrol inhibits Toxoplasma gondii-induced lung injury, inflammatory cascade and evidences of its mechanism of action.

BACKGROUND: Toxoplasma gondii is an opportunistic protozoan that can infect host to cause toxoplasmosis. We have previously reported that resveratrol (RSV) has protective effects against liver damage in T. gondii infected mice. However, the effect of RSV on lung injury caused by T. gondii infection and its mechanism of action remain unclear. PURPOSE: In this work, we studied the protective effects of RSV on lung injury caused by T. gondii infection and explored the underlying mechanism. METHODS: Molecular docking and localized surface plasmon resonance assay were used to detect the molecular interactions between RSV and target proteins. In vitro, the anti-T. gondii effects and potential anti-inflammatory mechanisms of RSV were investigated by quantitative competitive-PCR, RT-PCR, ELISA, Western blotting and immunofluorescence using RAW 264.7 cells infected with tachyzoites of T. gondii RH strain. In vivo, the effects of RSV on lung injury caused by T. gondii infection were assessed by observing pathological changes and the expression of inflammatory factors of lung. RESULTS: RSV inhibited T. gondii loads and T. gondii-derived heat shock protein 70 (T.g.HSP70) expression in RAW 264.7 cells and lung tissues. Moreover, RSV interacts with T.g.HSP70 and toll-like receptor 4 (TLR4), respectively, and interferes with the interaction between T.g.HSP70 and TLR4. It also inhibited the overproduction of inducible nitric oxide synthase, TNF-α and high mobility group protein 1 (HMGB1) by down-regulating TLR4/nuclear factor kappa B (NF-κB) signaling pathway, which is consistent with the effect of TLR4 inhibitor CLI-095. In vivo, RSV improved the pathological lung damage produced by T. gondii infection, as well as decreased the number of inflammatory cells in bronchoalveolar lavage fluid and the release of HMGB1 and TNF-α. CONCLUSION: These findings indicate that RSV can inhibit the proliferation of T. gondii and T.g.HSP70 expression both in vitro and in vivo. RSV can inhibit excessive inflammatory response by intervening T.g.HSP70 and HMGB1 mediated TLR4/NF-κB signaling pathway activation, thereby ameliorating lung injury caused by T. gondii infection. The present study provides new data that may be useful for the development of RSV as a new agent for the treatment of lung damage caused by T. gondii infection.

AANG Prevents Smad3-dependent Diabetic Nephropathy by Restoring Pancreatic ß-Cell Development in db/db Mice.

Diabetic nephropathy (DN) is a major cause of end-stage kidney disease, where TGF-ß1/Smad signaling plays an important role in the disease progression. Our previous studies demonstrated a combination of Traditional Chinese Medicine derived Smad7 agonist Asiatic Acid (AA) and Smad3 inhibitor Naringenin (NG), AANG, effectively suppressed the progression of renal fibrosis in vivo. However, its implication in type-2 diabetic nephropathy (T2DN) is still unexplored. Here, we detected progressive activation of Smad3 but reduction of Smad7 in db/db mice during T2DN development. Therefore, we optimized the dosage and the combination ratio of AANG to achieve a better rebalancing Smad3/Smad7 signaling for treatment of T2DN. Unexpectedly, preventive treatment with combined AANG from week 4 before the development of diabetes and T2DN effectively protected against the onset of T2DN. In contract, these inhibitory effects were lost when db/db mice received the late AANG treatment from 12-24 weeks. Surprisingly, preventive treatment with AANG ameliorated not only T2DN but also the primary disease type-2 diabetes (T2D) with relative normal levels of fasting blood glucose and HbA1c, and largely improving metabolic abnormalities especially on insulin insensitivity and glucose tolerance in db/db mice. Mechanistically, AANG effectively prevented both Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation in the diabetic kidney in vivo and advanced glycation end-products (AGE) stimulated tubular epithelial mTEC cells in vitro. More importantly, we uncovered that preventive treatment with AANG effectively protected against diabetic-associated islet injury via restoring the ß cell development in db/db mice. Taken together, we discovered that the early treatment with combined AANG can effectively protect against the development of T2D and T2DN via mechanism associated with protection against Smad3-depenedent islet injury.

Lonicerae japonicae flos ameliorates radiotherapy-induced mesenteric artery endothelial dysfunction through GTPCH1/BH4/eNOS pathway.

BACKGROUND: As a traditional Chinese medicine, Lonicerae japonicae flos (LJF) and its main component chlorogenic acid (CGA) have anti-oxidant, anti-bacterial and anti-tumor effects. However, there is no research on the potential of LJF for vascular protection in radiotherapy. PURPOSE: To elucidate the potential and possible mechanisms of the LJF extract and CGA in alleviating endothelial dysfunction caused by abdominal radiotherapy. METHODS: LJF was extracted with water and the CGA content was analyzed by HPLC. Male Sprague-Dawley rats received abdominal radiotherapy for 21 days. Seven days after irradiation, Laser Doppler and ex vivo vascular tension experiments were performed. Nitric oxide (NO), superoxide anion levels and tetrahydrobiopterin (BH4) content were detected. Western blot, flow cytometry and molecular docking were used. RESULTS: In the radiotherapy group, the mesenteric arterial blood perfusion, NO, and superoxide anion levels were significantly reduced; rats treated with the LJF extract or CGA showed a certain extent of recovery of these indicators. Vascular tension experiments showed that CGA and the LJF extract improved the vasodilation of mesenteric arteries. Cell experiments demonstrated that CGA increased the NO content and reduce superoxide anion production and cell apoptosis. The expression levels of GTPCH1/BH4/eNOS signaling pathway were significantly increased due to the use of the LJF extract or CGA in vivo and in vitro. CONCLUSIONS: Our study demonstrated for the first time that LJF and its main component, CGA could prevent abdominal radiotherapy-induced vascular endothelial dysfunction via GTPCH1/BH4/eNOS pathway. LJF could be a potential therapeutic herbal agent.

Selective Aerobic Oxidation of Csp3-H Bonds Catalyzed by Yeast-Derived Nitrogen, Phosphorus, and Oxygen Codoped Carbon Materials.

Nitrogen, phosphorus, and oxygen codoped carbon catalysts were successfully synthesized using dried yeast powder as a pyrolysis precursor. The yeast-derived heteroatom-doped carbon (yeast@C) catalysts exhibited outstanding performance in the oxidation of Csp3-H bonds to ketones and esters, giving excellent product yields (of up to 98% yield) without organic solvents at low O2 pressure (0.1 MPa). The catalytic oxidation protocol exhibited a broad range of substrates (38 examples) with good functional group tolerance, excellent regioselectivity, and synthetic utility. The yeast-derived heteroatom-doped carbon catalysts showed good reusability and stability after recycling six times without any significant loss of activity. Experimental results and DFT calculations proved the important role of N-oxide (N+-O-) on the surface of yeast@C and a reasonable carbon radical mechanism.

Traditional Chinese Medicine for HIV-Associated Acute Herpes Zoster: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Herpes zoster (HZ) is a common infection in individuals with acquired immunodeficiency syndrome (AIDS) patients. Traditional Chinese medicine (TCM) has been used widely in clinical practice for HZ, which remains not supportive of evidence. This review aimed to evaluate the effectiveness and safety of TCM in treating HIV-associated HZ. METHODS: Nine electronic databases were searched for randomized controlled trials (RCTs) testing TCM in treating HIV-associated HZ. Data were extracted on citations, interventions, and outcomes, by two authors independently. For the quality evaluation, Cochrane risk-of-bias tool 2.0 was used. Meta-analyses were performed by Revman5.3 software. Effect estimation presented as risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data with their 95% confidence interval (CI). RESULTS: Twelve RCTs (n = 644) were included; the majority of them had a high or unclear risk of bias. Meta-analysis showed that pain intensity (VAS 0-5) in the Chinese herbal medicine (CHM) group was lower than it in the drugs group (MD = -0.87, 95% CI [-1.69, -0.04], two trials, n = 93). Duration of herpes-related pain (days) of patients in the combination group was shorter than those in the drugs group (MD = -9.19, 95% CI [-16.73, -1.65], n = 144). The incidence of postherpetic neuralgia (PHN) in the combination group was lower than in the drugs group (RR = 0.49, 95% CI [0.25, 0.99], n = 202). As for cure rate (complete absence of pain and herpes), two trials showed that CHM was better than drugs (RR = 1.58, 95% CI [1.13, 2.22], n = 93), five trials showed combination treatment was better than drugs (RR = 1.40, 95% CI [1.08, 1.82], n = 224). The cure rate in the acupuncture group was more than that in the drugs group (RR = 1.99, 95% CI [1.18, 3.36], n = 120). Four trials reported adverse effects and found no serious adverse events occurred. CONCLUSION: CHM and acupuncture demonstrate more benefits than drugs in pain relief, cure rate improvement, and incidence reduction of PHN. However, given the data limitation and TCM therapies' diversity, the conclusions need to be verified in future trials.

A proposed approach to confirm heroin administration - Regional differences in heroin purity is a major factor.

In forensic toxicology, a marker of street heroin use is urgent especially in the absence of urinary 6-monoacetylmorphine. ATM4G, the Glucuronide of Acetylated product of Thebaine compound 4 Metabolite (ATM4), arising from byproducts of street heroin synthesis has been considered as a useful marker in some European studies. However, whether ATM4G is a universal marker particularly in Southeast Asia due to 'street' heroin with high purity, it's still unclear. To investigate putative markers for different regions, ATM4G and other metabolites including the Acetylated product of Thebaine compound 3 Metabolite (ATM3) and thebaol, also originated from thebaine were detected in 552 urine samples from heroin users in Taiwan. Results were compared with that from samples collected in the UK and Germany. Only a sulfo-conjugate of ATM4, ATM4S, was detected in 28 Taiwanese users using a sensitive MS3 method whilst out of 351 samples from the UK and Germany, ATM4G was present in 91. Thebaol-glucuronide was first time detected in 118. No markers were detected in urine following herbal medicine use or poppy seed ingestion. The presence of ATM4S/ATM4G might be affected by ethnicities and heroin supplied in regions. Thebaol-glucuronide is another putative marker with ATM4G and ATM4S for street heroin use.

Smad3-Targeted Therapy Protects against Cisplatin-Induced AKI by Attenuating Programmed Cell Death and Inflammation via a NOX4-Dependent Mechanism.

BACKGROUND: Transforming growth factor-ß (TGF-ß)/Smad signaling is the central mediator in renal fibrosis, yet its functional role in acute kidney injury (AKI) is not fully understood. Recent evidence showed that TGF-ß/Smad3 may be involved in the pathogenesis of AKI, but its functional role and mechanism of action in cisplatin-induced AKI are unclear. OBJECTIVES: Demonstrating that Smad3 may play certain roles in cisplatin nephropathy due to its potential effect on programmed cell death and inflammation. METHODS: Here, we established a cisplatin-induced AKI mouse model with Smad3 knockout mice and created stable in vitro models with Smad3 knockdown tubular epithelial cells. In addition, we tested the potential of Smad3-targeted therapy using 2 in vivo protocols - lentivirus-mediated Smad3 silencing in vivo and use of naringenin, a monomer used in traditional Chinese medicine and a natural inhibitor of Smad3. RESULTS: Disruption of Smad3 attenuated cisplatin-induced kidney injury, inflammation, and NADPH oxidase 4-dependent oxidative stress. We found that Smad3-targeted therapy protected against loss of renal function and alleviated apoptosis, RIPK-mediated necroptosis, renal inflammation, and oxidative stress in cisplatin nephropathy. CONCLUSIONS: These findings show that Smad3 promotes cisplatin-induced AKI and Smad3-targeted therapy protects against this pathological process. These findings have substantial clinical relevance, as they suggest a therapeutic target for AKI.

Traditional Chinese medicine for COVID-19 pandemic and emerging challenges: An online cross-sectional survey in China.

BACKGROUND: We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. METHODS: The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. RESULTS: The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics; 16 (35.6%) used TCM interventions(s); while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. CONCLUSION: We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

AANG: A natural compound formula for overcoming multidrug resistance via synergistic rebalancing the TGF-ß/Smad signalling in hepatocellular carcinoma.

Cancer cells are high in heterogeneity and versatility, which can easily adapt to the external stresses via both primary and secondary resistance. Targeting of tumour microenvironment (TME) is a new approach and an ideal therapeutic strategy especially for the multidrug resistant cancer. Recently, we invented AANG, a natural compound formula containing traditional Chinese medicine (TCM) derived Smad3 inhibitor Naringenin (NG) and Smad7 activator Asiatic Acid (AA), for rebalancing TGF-ß/Smad signalling in the TME, and its implication on the multidrug resistance is still unexplored. Here, we observed that an equilibrium shift of the Smad signalling in patients with hepatocellular carcinoma (HCC), which was dramatically enhanced in the recurrent cases showing p-glycoprotein overexpression. We optimized the formula ratio and dosage of AANG that effectively inhibit the proliferation of our unique human multidrug resistant subclone R-HepG2. Mechanistically, we found that AANG not only inhibits Smad3 at post-transcriptional level, but also upregulates Smad7 at transcriptional level in a synergistic manner in vitro. More importantly, AANG markedly suppressed the growth and p-glycoprotein expression of R-HepG2 xenografts in vivo. Thus, AANG may represent a novel and safe TCM-derived natural compound formula for overcoming HCC with p-glycoprotein-mediated multidrug resistance.

Therapeutic effects and safety of oral Chinese patent medicine for COVID-19: A rapid systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Chinese patent medicine (CPM) is an indispensable part of traditional Chinese medicine. Coronavirus Disease 2019 (COVID-19) manifests is an acute respiratory infectious disease. This systematic review aimed to evaluate the therapeutic effects and safety of oral CPM for COVID-19. METHODS: We included randomized controlled trials (RCTs) that tested oral CPM for the treatment of COVID-19 identified from publications in CNKI, Wanfang, VIP, Web of Science, SinoMed, PubMed, Embase, BioRxiv, MedRxiv and arXiv before November 2nd, 2020. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Seven RCTs including 1079 participants were identified. The overall bias was assessed as "-high risk of bias" for all included trials. Oral CPM investigated were: Lianhua Qingwen capsule/granules (LHQW), Jinhua Qinggan granules (JHQG), Huoxiang Zhengqi dripping pills (HXZQ), Toujie Quwen granules (TJQW) and Lianhua Qingke granules (LHQK). Compared with conventional western therapy alone for people with COVID-19: regarding the main outcomes, the results showed that oral CPM combined with conventional western therapy improved cure rate (RR = 1.20, 95 % CI 1.04-1.38, involving LHQW and TJQW), reduced aggravation rate (RR = 0.50, 95 % CI 0.29 - 0.85, involving LHQW, JHQG, LHQK and TJQW); with regard to additional outcomes, the results showed that add-on oral CPM shortened the duration of fever, cough and fatigue, improved the recovery rate of cough and fatigue, and increased the improvement and recovery rate of chest CT manifestations. There were some differences in therapeutic effects among various CPMs for the same COVID-19 outcome. The use of TJQW and LHQG appeared not to increase the risk of adverse events, but JHQG may cause mild diarrhea. CONCLUSION: Low-certainty or very low-certainty evidence demonstrated that oral CPM may have add-on potential therapeutic effects for patients with non-serious COVID-19. These findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.

Bupleuri radix for Acute Uncomplicated Respiratory Tract Infection: A Systematic Review of Randomized Controlled Trials.

Objective: To evaluate the efficacy, clinical effectiveness, and safety of the Chinese herb Bupleuri radix for the treatment of acute uncomplicated respiratory tract infections (ARTIs). Methods: Four English and four Chinese databases were searched from their inception to June 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of Bupleuri radix on ARTI were eligible for inclusion. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses with effects estimated as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). The certainty of the evidence was assessed using the online GRADEpro tool. Results: Seven randomized trials involving 910 patients with acute upper respiratory tract infection (AURTI) were included. The review identified Bupleuri radix agents with four administration routes (oral, acupoint injection, intramuscular injection, nebulized inhalation). Bupleuri radix acupoint injection compared with placebo showed statistically significant effects in reducing fever resolution time (MD: -33.32 h, 95%CI: -35.71, -30.93), and in increasing the proportion of participants with fever resolved within 48 h from treatment onset (RR: 14, 95%CI: 1.96, 99.94). Bupleuri radix acupoint injection combined with usual care is more effective in reducing the temperature at day 1 from treatment onset (MD: -1.00°C, 95%CI: -1.19, -0.81) compared with usual care alone. Bupleuri radix pills showed similar antipyretic effects to acetaminophen. However, Bupleuri radix intramuscular injection plus vitamins failed to demonstrate an effect in reducing fever, when compared with ribavirin plus vitamins. It suggested that oral administration of Bupleuri radix solution for injections, pills, and Bupleuri radix decoction have a similar effect on improving global AURTI symptoms including two key symptoms (nasal discharge and cough), when compared with usual care alone. Only two trials reported whether or not there were any AEs and found no occurrence of adverse events in the herbal group. Conclusion: Low-certainty or very low-certainty evidence demonstrated that Bupleuri radix (solution for injections and pills) has an antipyretic effect on febrile patients with AURTI, but it has no effect on other AURTI symptoms. However, these findings need to be further confirmed by well-designed clinical trials with adequate sample sizes. Systematic review registration: (https://www.crd.york.ac.uk/prospero/#recordDetails), PROSPERO registration number: CRD42021234066.

Novel Bithiophene Dimers from Echinops latifolius as Potential Antifungal and Nematicidal Agents.

Three novel dimeric bithiophenes, echinbithiophenedimers A-C (1-3), along with two known thiophenes, 4 and 5, were obtained from Echinops latifolius, and their structures were identified through extensive spectroscopic analysis and electronic circular dichroism calculations. Compounds 1-3 possessed new carbon skeletons; they are dimeric bithiophenes with 1 and 2 featuring an unprecedented 1,3-dioxolane ring system and 3 featuring an unusual 1,4-dioxane ring. These compounds are the first examples of bithiophene dimers furnished by different cyclic diethers. Dimeric bithiophenes 1-3 had good antifungal activities against five phytopathogenic fungi, and compound 3 showed excellent activity against Alternaria alternate and Pyricularia oryzae, with a minimal inhibitory concentration value of 8 µg/mL, which was close to or higher than that of carbendazim. Moreover, its effect on the mycelial morphology was observed by scanning electron microscopy. Compounds 1-3, which were demonstrated to be nonphototoxic thiophenes, exhibited better nematicidal activity than the commercial nematicide ethoprophos against Meloidogyne incognita. This study revealed that dimeric bithiophenes containing 1,3-dioxolane or 1,4-dioxane rings could be used as novel antifungal and nematicidal agents for controlling plant fungal and nematode pathogens.

Eucalyptus essential oils inhibit the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through reducing MAPK and NF-κB pathways.

BACKGROUND: Eucalyptus essential oils have been used in traditional medicine for centuries. It was reported that Eucalyptus leaves possess antioxidant and antimicrobial effects. Here, we investigated the anti-inflammatory activity of the essential oils extracted from the leaves of four different Eucalyptus species in RAW264.7 macrophages. METHODS: Lipopolysaccharide (LPS)-activated RAW264.7 macrophages were used to evaluate the anti-inflammatory activity of the leaf essential oils of Eucalyptus. The cell survival was quantified by an Alamar Blue assay. Nitric oxide (NO) production was assessed by Griess reaction. TNF-α and IL-6 production were measured by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-κB (NF-κB) transcriptional activity was measured by NF-κB reporter assay. Intracellular protein expression levels were determined by Western blot. The expression levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and NF-κB pathway were measured by western blot in LPS-activated RAW 264.7 macrophage. RESULTS: The essential oils extracted from Eucalyptus citriodora leaf exert the best NO inhibitory activity in LPS-activated RAW264.7 macrophages. The essential oils were fractionated into fractions A-H, and fraction F has been demonstrated to inhibit the expression levels of TNF-α, IL-6, NO, iNOS and COX-2 in LPS-activated RAW264.7 macrophages. Mechanistic analysis revealed that fraction F reduced the phosphorylation levels of ERK1/2, p38, PKC-α, PKC-ε and PKC-δ, and inhibited the NF-κB transcriptional activity. The chemical composition of Fraction F was determined by GC-MS. CONCLUSIONS: The discoveries made herein could help develop innovative nonsteroidal anti-inflammatory drugs with minimal side effects and strong efficacy. Clinical trials on these Eucalyptus leaf essential oils will help customize and optimize their therapeutic administration.

Quercetin protects against cisplatin-induced acute kidney injury by inhibiting Mincle/Syk/NF-κB signaling maintained macrophage inflammation.

Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF-κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL-1ß, IL-6, and TNF-α in LPS-induced bone marrow-derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF-κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL-1ß, IL-6, and TNF-α in cisplatin-induced AKI model. Furthermore, quercetin down-regulated protein levels of Mincle, phosphorylated Syk and NF-κB in kidney macrophages of AKI, as well as inhibited M1, up-regulated M2 macrophage activity. Notably, the down-regulation of LPS-induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI-induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.

Petchiether A attenuates obstructive nephropathy by suppressing TGF-ß/Smad3 and NF-κB signalling.

Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor-ß1 (TGF-ß1)/Smad3-driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small-molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF-ß1-induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin-1ß and tumour necrosis factor-α) and reducing extracellular matrix deposition (α-smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF-κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down-regulated the expression of the fibrotic marker collagen I in TGF-ß1-treated renal epithelial cells. Further, we found that petA dose-dependently suppressed Smad3-responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF-ß/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF-ß/Smad3 signalling.