The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Therapeutic and immune-regulation effects of Scutellaria baicalensis Georgi polysaccharide on pseudorabies in piglets.

Pseudorabies virus (PRV) can cause fatal encephalitis in newborn pigs and escape the immune system. While there is currently no effective treatment for PRV, Scutellaria baicalensis Georgi polysaccharides (SGP) and Rodgersia sambucifolia Hemsl flavonoids (RHF) are traditional Chinese herbal medicines with potential preventive and therapeutic effects against PRV infection. In order to explore which one is more effective in the prevention and treatment of PRV infection in piglets. We investigate the therapeutic effects of RHF and SGP in PRV-infected piglets using clinical symptom and pathological injury scoring systems. The immune regulatory effects of RHF and SGP on T lymphocyte transformation rate, cytokines, T cells, and Toll-like receptors were also measured to examine the molecular mechanisms of these effects. The results showed that SGP significantly reduced clinical symptoms and pathological damage in the lungs, liver, spleen, and kidneys in PRV-infected piglets and the T lymphocyte conversion rate in the SGP group was significantly higher than that in the other treatment groups, this potential dose-dependent effect of SGP on T lymphocyte conversation. Serum immunoglobulin and cytokine levels in the SGP group fluctuated during the treatment period, with SGP treatment showing better therapeutic and immunomodulatory effects in PRV-infected piglets than RHF or the combined SGP + RHF treatment. In conclusion, RHF and SGP treatments alleviate the clinical symptoms of PRV infection in piglets, and the immunomodulatory effect of SGP treatment was better than that of the RHF and a combination of both treatments. This study provides evidence for SGP in controlling PRV infection in piglets.

[Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury].

OBJECTIVE: To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury. METHODS: Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side. RESULTS: Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group. CONCLUSION: Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

San Huang Xiao Yan recipe modulates the HMGB1-mediated abnormal inflammatory microenvironment and ameliorates diabetic foot by activating the AMPK/Nrf2 signalling pathway.

BACKGROUND: Diabetic foot (DF) is one of the serious complications of diabetes and lacks of therapeutic drugs. Abnormal and chronic inflammation promoting foot infection and wound healing delay are the main pathogenesis of DF. The traditional prescription San Huang Xiao Yan Recipe (SHXY) has been used in the clinical treatment of DF for several decades as approved hospital experience prescription and showed remarkable therapeutic effect, but the mechanisms by which SHXY treats DF are still unclear. PURPOSE: Objectives of this study were to investigate SHXY anti-inflammatory effect on DF and explore the molecular mechanism for SHXY. METHODS: We detected the effects of SHXY on DF in C57 mouse and SD rat DF models. Animal blood glucose, weight and wound area were detected every week. Serum inflammatory factors were detected by ELISA. H&E and Masson's trichrome were used to observe tissue pathology. Single-cell sequencing data reanalysis revealed the role of M1 macrophages in DF. Venn analysis showed the co-target genes between DF M1 macrophages and compound-disease network pharmacology. Western blotting was used to explored target protein expression. Meanwhile, RAW264.7 cells were treated with drug-containing serum of SHXY to further unravel the roles of target proteins during high glucose-induced inflammation in vitro. The Nrf2 inhibitor ML385 was used on RAW 264.7 cells to further explore the relationship between Nrf2, AMPK and HMGB1. The main components of SHXY were analysed by HPLC. Finally, the treatment effect of SHXY on DF were detected on rat DF model. RESULTS: In vivo, SHXY can ameliorate inflammatory, accelerate wound healing and upregulate expression of Nrf2, AMPK and downregulate of HMGB1. Bioinformatic analysis showed that M1 macrophages were the main inflammatory cell population in DF. Moreover, the Nrf2 downstream proteins HO-1 and HMGB1 were potential DF therapeutic targets for SHXY. In vitro, we also found that SHXY increased AMPK and Nrf2 protein levels and downregulated HMGB1 expression in RAW264.7 cells. Inhibiting the expression of Nrf2 impaired the inhibition effect of SHXY on HMGB1. SHXY promoted Nrf2 translocation into the nucleus and increased the phosphorylation of Nrf2. SHXY also inhibited HMGB1 extracelluar release under high glucose. In rat DF models, SHXY also exhibited significant anti-inflammatory effect. CONCLUSION: The SHXY activated AMPK/Nrf2 pathway to suppress abnormal inflammation on DF via inhibiting HMGB1 expression. These findings provide novel insight into the mechanisms by which SHXY treats DF.

The efficacy and safety of acupuncture therapy for sciatica: A systematic review and meta-analysis of randomized controlled trails.

Background and objective: Sciatica is a common type of neuropathic pain disease which poses a huge financial burden to the patient. For patients with sciatica, acupuncture has been recommended as an effective method for pain relief, while there is currently a lack of sufficient evidence to support its efficacy and safety. In this review, we aimed to critically assess the published clinical evidence on the efficacy and safety of acupuncture therapy for treating sciatica. Methods: An extensive literature search strategy was established in seven databases from their inception to 31 March 2022. Two independent reviewers performed the literature search, identification, and screening. Data extraction was performed on studies that meet the inclusion criteria, and a further quality assessment was performed according to the Cochrane Handbook and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) recommendations. Summary Risk ratio (RR) and standardized mean differences (SMDs) with 95% confidence interval (CI) were calculated using the fixed-effects or the random-effects model. Heterogeneity in effect size across studies was explored using the subgroup analysis and the sensitivity analysis. The quality of evidence was estimated following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: A total of 30 randomized controlled trials (RCTs) involving 2,662 participants were included in the meta-analysis. The results of the integration of clinical outcomes showed that the clinical efficacy of acupuncture was superior to that of medicine treatment (MT) in improving the total effective rate (relative risk (RR) = 1.25, 95% confidence interval (CI) [1.21, 1.30]; moderate certainty of evidence), reducing the Visual Analog Scale (VAS) pain score (standardized mean difference (SMD) = -1.72, 95% CI [-2.61, -0.84]; very low certainty of evidence), increasing pain threshold (SMD = 2.07, 95% CI [1.38, 2.75]; very low certainty of evidence), and decreasing recurrence rate (RR = 0.27, 95% CI [0.13, 0.56]; low certainty of evidence). In addition, a few adverse events (RR = 0.38, 95% CI [0.19, 0.72]; moderate certainty of evidence) were reported during the intervention, which indicated that acupuncture was a safe treatment option. Conclusions: Acupuncture therapy is an effective and safe treatment for patients with sciatica, and it can be considered a suitable replacement for medicine treatment (MT). However, given the high heterogeneity and a low methodological quality of previous studies, future RCTs should be well-designed according to the rigorous methodology. Systematic review registration: International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) (https://inplasy.com/register/), identifier [INPLASY202240060].

Circadian signatures of anterior hypothalamus in time-restricted feeding.

Background: Meal timing resets circadian clocks in peripheral tissues, such as the liver, in seven days without affecting the phase of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Anterior hypothalamus plays an essential role in energy metabolism, circadian rhythm, and stress response. However, it remains to be elucidated whether and how anterior hypothalamus adapts its circadian rhythms to meal timing. Methods: Here, we applied transcriptomics to profile rhythmic transcripts in the anterior hypothalamus of nocturnal female mice subjected to day- (DRF) or night (NRF)-time restricted feeding for seven days. Results: This global profiling identified 128 and 3,518 rhythmic transcripts in DRF and NRF, respectively. NRF entrained diurnal rhythms among 990 biological processes, including 'Electron transport chain' and 'Hippo signaling' that reached peak time in the late sleep and late active phase, respectively. By contrast, DRF entrained only 20 rhythmic pathways, including 'Cellular amino acid catabolic process', all of which were restricted to the late active phase. The rhythmic transcripts found in both DRF and NRF tissues were largely resistant to phase entrainment by meal timing, which were matched to the action of the circadian clock. Remarkably, DRF for 36 days partially reversed the circadian clock compared to NRF. Conclusions: Collectively, our work generates a useful dataset to explore anterior hypothalamic circadian biology and sheds light on potential rhythmic processes influenced by meal timing in the brain (www.circametdb.org.cn).

Epigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2.

BACKGROUND: Targeting helper T cells, especially Th17 cells, has become a plausible therapy for many autoimmune diseases. METHODS: Using an in vitro culture system, we screened an epigenetics compound library for inhibitors of IFN-γ and IL-17 expression in murine Th1 and Th17 cultures. FINDINGS: This identified IOX1 as an effective suppressor of IL-17 expression in both murine and human CD4+ T cells. Furthermore, we found that IOX1 suppresses Il17a expression directly by targeting TET2 activity on its promoter in Th17 cells. Using established pre-clinical models of intraocular inflammation, treatment with IOX1 in vivo reduced the migration/infiltration of Th17 cells into the site of inflammation and tissue damage. INTERPRETATION: These results provide evidence of the strong potential for IOX1 as a viable therapy for inflammatory diseases, in particular of the eye. FUNDING: This study was supported by the National Key Research and Development Program of China 2021YFA1101200 (2021YFA1101204) to LW and XW; the National Natural Science Foundation of China 81900844 to XH and 82171041 to LW; the China Postdoctoral Science Foundation 2021M700776 and the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine 20221373 to YZ; and the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS (National Health Service) Foundation Trust and University College London Institute of Ophthalmology, UK (DAC, LPS, PJPL, MS, ADD and RWJL). The views expressed are those of the authors and not necessarily those of the NIHR or the UK's Department of Health and Social Care.

[The Prognosis Assessment Value of Interim 18F-FDG PET/CT Imaging in the Chemotherapy of Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the prognostic value of interim 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (△SUVmax%) cut-off value. The prognostic value of △SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum △SUV max% cut-off value was 74.9%. Patients with △SUVmax%≥74.9% had a lower rate of progression or recurrence than those with △SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). △SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). △SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), △SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that △SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION: Both 5-PS and △SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of △SUVmax% is superior to that of 5-PS.

Dexmedetomidine Mitigates Myocardial Ischemia/Reperfusion-Induced Mitochondrial Apoptosis through Targeting lncRNA HCP5.

Our study aimed to explore the function and mechanism of Dexmedetomidine (Dex) in regulating myocardial ischemia/reperfusion (I/R)-induced mitochondrial apoptosis through lncRNA HCP5. We demonstrated Dex suppressed I/R-induced myocardial infarction and mitochondrial apoptosis in vivo. Dex induced the expression of lncRNA HCP5 and MCL1, inhibited miR-29a expression and activated the JAK2/STAT3 signaling. Dex attenuated hypoxia/reoxygenation (H/R)-induced mitochondrial apoptosis by upregulating lncRNA HCP5 in cardiomyocytes. Overexpression of lncRNA HCP5 sponged miR-29a to suppress H/R-induced mitochondrial apoptosis. Knockdown of miR-29a also alleviated cardiomyocyte apoptosis by upregulating MCL1. Overexpression of lncRNA HCP5 activated the JAK2/STAT3 signaling through sponging miR-29a and enhancing MCL1 expression in cardiomyocytes. Dex mitigated myocardial I/R-induced mitochondrial apoptosis through the lncRNA HCP5/miR-29a/MCL1 axis and activation of the JAK2/STAT3 signaling.

Hydrolytically Stable Zr-Based Metal-Organic Framework as a Highly Sensitive and Selective Luminescent Sensor of Radionuclides.

Effective detections of radionuclides including uranium and its predominant fission products, for example, iodine, are highly desired owing to their radiotoxicity and potential threat to human health. However, traditional analytical techniques of radionuclides are instrument-demanding, and chemosensors targeted for sensitization of radionuclides remain limited. In this regard, we report a sensitive and selective sensor of UO22+ and I- based on the unique quenching behavior of a luminescent Zr-based metal-organic framework, Zr6O4(OH)4(OH)6(H2O)6(TCPE)1.5·(H2O)24(C3H7NO)9 (Zr-TCPE). Immobilization of the luminescent tetrakis(4-carboxyphenyl)ethylene (TCPE4-) linkers by Zr6 nodes enhances the photoluminescence quantum yield of Zr-TCPE, which facilitates the effective sensing of radionuclides in a "turn-off" manner. Moreover, Zr-TCPE can sensitively and selectively recognize UO22+ and I- ions with the lowest limits of detection of 0.67 and 0.87 µg/kg, respectively, of which the former one is much lower than the permissible value (30 µg/L) defined by the U.S. EPA. In addition, Zr-TCPE features excellent hydrolytic stability and can withstand pH conditions ranging from 3 to 11. To facilitate real-world applications, we have further fabricated polyvinylidene fluoride-integrating Zr-TCPE as luminescence-based sensor membranes for on-site sensing of UO22+ and I-.

Efficacy and potential mechanisms of Chinese herbal compounds in coronavirus disease 2019: advances of laboratory and clinical studies.

The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms and outcomes in patients with COVID-19, particularly together with routine treatment strategy. The pharmacological activities were mainly attributed to the relief of clinical symptoms, inhibition of cytokine storm, and improvement of organ function. Besides, the development of novel antiviral drugs from medicinal herbs were further discussed. The updated laboratory and clinical studies provided the evidence of Chinese herbal compounds such as Lianhua Qingwen prescription, Shufeng Jiedu prescription, and Qingfei Paidu Tang for the relief of COVID-19. However, both of the randomized controlled trials and real world researches need to be done for supporting the evidence including the efficacy and safety in fighting COVID-19.

[A novel pathogenic Colletotrichum species for rhizome rot disease of Polygonatum kingianum].

Rhizome rot disease is one of the main disease of planted Polygonatum kingianum. In this study, six strains of pathogenic fungus was isolated from P. kingianum samples with rhizome rot disease collected from six counties in Yunnan province. Its pathogenicity was confirmed by inoculation to healthy P. kingianum rhizome according to Koch's postulates. The colonies of the isolated fungi on potato dextrose agar(PDA) were orange with abundant crescentic conidia which were eseptate with a mean size of 19. 3-24. 9 µm×5. 2-5. 9 µm and a L/W ratio of 3. 4-4. 5. There was an oil ball in the center of the conidium. It's easy to see setae on PDA colony.The phylogenetic tree based on ITS, GAPDH, CHS-1, HIS3, ACT, and TUB2 sequences by maximum likelihood(ML) method indicated that the pathogenic fungus for P. kingianum rhizome rot disease was clustered into the clade of Colletotrichum spaethianum species complex, and was close to C. spaethianum. However, there were some differences in morphological and genetic characteristics between the pathogenic fungus and C. spaethianum. Therefore, the pathogenic fungus for rhizome rot disease of P. kingianum was identified as a new Colletotrichum species named C. kingianum. The disease spreads primarily due to the plantation of infected seedlings of P. kingianum. It is necessary to choose healthy seedlings and take rigorous disinfection measures for the disease prevention.

The Protective Effect of Ethyl Acetate and n-Butanol Fractions of Wine-Steamed Ligustri Lucidi Fructus on Diabetic Nephropathy in Rats.

Ligustri Lucidi Fructus (LLF), the dry and ripe fruit of Ligustrum lucidum W. T. Aiton (Oleaceae), is a traditional Chinese medicine for nourishing the liver and kidney in clinics for thousands of years. Wine-steamed Ligustri Lucidi Fructus (WLL) can alleviate coolness and smoothness of LLF and enhance the function of nourishing the liver and kidney, so ancient and modern medicine usually used it in clinics. First of all, we prepared the extracts of different polar fractions of WLL to explore the effective fractions and potential mechanisms of WLL in the treatment of diabetic nephropathy (DN). Then, HPLC method was used to determine the contents of 12 active components in WLL and its different polar components. Finally, the potential relationship between 12 active components and physicochemical parameters of DN rats was explored. The pharmacological experiments showed that WLL, ethyl acetate (EtOAc), and n-butanol (n-BuOH) extracts not only significantly alleviated the clinical symptoms and kidney damage of DN rats but also had obvious anti-inflammatory and antioxidant effects. In addition, the results of HPLC analysis showed that the 12 active components of WLL mainly existed in the extracts of EtOAc and n-BuOH. The Pearson correlation analysis showed 12 active components and physicochemical parameters had different degrees of correlation. In conclusion, we proved that the extracts of EtOAc and n-BuOH were the effective fractions of WLL in treating DN in rats, and they could regulate the levels of inflammatory cytokines and decrease oxidation stress, which provides a basis for further research on the mechanism of WLL in treating DN and provides a pharmacological and chemical foundation for the development of new anti-DN drugs.

Chinese herbal injections for coronavirus disease 2019 (COVID-19): A narrative review.

BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) has caused more than 180 million infections and 3.9 million deaths. To date, emerging clinical evidence has shown the synergetic benefits of Chinese herbal injections in treating this contagious respiratory disease. This review aims to summarize and analyze the efficacy and safety of Chinese herbal injections in the therapy of COVID-19. METHODS: The literature from 3 electronic databases, PubMed, CNKI, and Web of Science, were searched using the search terms "COVID-19", "SARS-CoV-2", "traditional Chinese medicine", "herb", "herbal", and "injection". Then the identified articles were comprehensively evaluated. RESULTS: Limited data demonstrated that Chinese herbal injections could significantly improve the clinical outcomes of COVID-19 patients, especially in combination with conventional treatment strategies. The benefits of which were mainly associated with the relief of symptoms, prevention of secondary infection, regulation of inflammation and immune function. There was also evidence showing the inhibitory effects on SARS-CoV-2 replication in vitro. Nevertheless, available real-world data suggested the increased risk of adverse event. Furthermore, the defects of existing researches and the insights for discovering novel antiviral drugs were prospectively discussed. CONCLUSION: Evidence-based advances revealed that Chinese herbal injections such as XueBiJing injection and ShenMai injection, exerted potent effects against COVID-19. Further laboratory researches and clinical evaluation are needed to gather scientific evidence on the efficacy and safety.

[Acupuncture intervention prolongates thrombolysis time window by regulating cerebral cortex angiogenesis-related genes and proteins in cerebral infarction rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (Endostatin, ES) mRNAs and proteins (angiogenesis related factors) in the ischemic penumbra region in rats with cerebral infarction (CI), so as to explore its underlying mechanisms in prolonging the time window of thrombolysis therapy for CI. METHODS: A total of 48 male SD rats were randomly divided into sham operation, model, medication (6 h thrombolysis) and acupuncture (Acupunct)+medication groups (n=12 in each group). The CI model was established using modified auto-thrombus method. Six hours after thrombolysis, recombinant human tissue plasminogen activator (rt-PA,10 mg/kg) was given to rats of the thrombolysis group through tail vein. Acupuncture was applied at "Shuigou"(CV26) and bilateral "Neiguan" (PC6) 2 h after successful modeling, and the needles were retained for 30 minutes. Cerebral blood flow (CBF) was monitored during modeling in each group, and the neurological deficit score (0-7 points) was given 2 h and 24 h after successful modeling according to Bederson's methods. The cerebral infarction volume was observed after triphenyltetrazole chloride (TTC) staining. The protein and mRNA expression levels of VEGF, bFGF and ES in the ischemic penumbra region of the right cerebral cortex were detected by Western blot and real-time PCR, separately. RESULTS: The neurological deficit score at both 2 h and 24 h after modeling, percentage of cerebral infarction volume, and the expression levels of VEGF, bFGF and ES proteins and mRNAs in the model group were significantly higher than those of the sham operation group (P<0.01, P < 0.05). Compared with the model group, the neurological deficit score 24 h (not at 2 h) after modeling and percentage of cerebral infarction volume, and the expression levels of ES protein and mRNA in the Acupunct+medication group (not in the medication group) were notably lower (P<0.05, P<0.01), while the expression levels of VEGF and bFGF proteins and mRNAs in the Acupunct +medication group (not in the medication group) were considerably higher (P<0.01, P<0.05). No significant differences were found between medication and model groups in the CI percentage, VEGF, bFGF and ES proteins and mRNAs (P>0.05). The therapeutic effect of Acupunct +medication group was significantly superior to that of medication in lowering neurological deficit score, percentage of CI volume and expression of ES protein and mRNA and in up-regulating the expression of VEGF and bFGF proteins and mRNAs (P<0.05, P<0.01). CONCLUSION: Acupuncture and timely intervention can prolong the time window of thrombolysis in CI rats, which may be related to its function in up-regulating the expression of VEGF and bFGF mRNAs and proteins and in down-regulating the expression of ES mRNA and protein in ischemic cerebral cortex.

[Thrombolysis combined with acupuncture therapy for acute cerebral infarction: a Meta-analysis of randomized controlled trials].

OBJECTIVE: To systematically evaluate the efficacy and safety of thrombolysis combined with acupuncture therapy in the treatment of acute cerebral infarction (ACI) in the light of evidence-based medicine. METHODS: Randomized controlled trials (RCT) for acupuncture and thrombolysis treatment of acute cerebral infarction published from the inception of databa-ses to March 2020 were searched from PubMed, Cochrane Library, Embase, Web of science, CNKI, Wanfang, VIP, and CBM Database. According to the inclusion and exclusion criteria, two reviewers independently screened the RCTs and extracted the data. The quality of the included literature was evaluated, and the Meta-analysis was performed by using Revman 5.3 software. RESULTS: A total of 330 studies were identified, and 14 RCTs (including 604 cases of the treatment group, 598 cases of the control group) met the inclusion criteria. The Meta-analysis showed that the thrombolysis combined with acupuncture therapy was better than acupuncture therapy alone in the clinical effective rate (risk ratio ï¼»RRï¼½=1.19, 95% confidence interval ï¼»CIï¼½ ï¼»1.13, 1.25ï¼½), NIHSS score (mean difference ï¼»MDï¼½=-3.51, 95% CI ï¼»-4.54, -2.48ï¼½), BI index (MD=12.26, 95% CI ï¼»8.07, 16.46ï¼½), and in lowering C-reaction protein levels (MD=-3.99, 95% CI ï¼»-4.35, -3.63ï¼½). The rate of complete recanalization (RR = 1.20, 95% CI ï¼»1.00, 1.44ï¼½), adverse reaction (RR = 0.76, 95% CI ï¼»0.41, 1.41ï¼½) and hemorrhagic conversion (RR = 0.72, 95% CI ï¼»0.14, 3.62ï¼½) was not statistically significant. CONCLUSION: The current effective evidence shows that acupuncture has certain advantages in improving the therapeutic effect and safety of thrombolysis in the treatment of ACI patients.

Herbal formula of Bushen Jianpi combined with sorafenib inhibits hepatocellular carcinoma growth by promoting cell apoptosis and blocking the cell cycle.

OBJECTIVE: To investigate the efficacy of an herbal formula of Bushen Jianpi ( BSJP) combined with sorafenib on hepatocellular carcinoma (HCC) in vitro and in vivo, and to study the underlying mechanisms of action. METHODS: BSJP, a mixture of 12 raw herbs, was extracted in 70% alcohol/30% water and freeze-dried into a powder. The in vitro effects of BSJP alone, sorafenib alone, and their combination on cell survival, apoptosis, and cell cycle distribution were evaluated in HCC cell lines HCCLM3, HepG2, and SMMC-7721. The expression of B-cell lymphoma-2 (Bcl-2), caspase-3, and caspase-9 in HCCLM3 cells was measured using Western blots after drug administration. The in vivo effects of BSJP and sorafenib were evaluated in a tumor surgical resection model using 4-week old male athymic BALB/c nude mice injected with HCCLM3 cells. Immunohistochemical analysis of tumor tissues was performed to evaluate the effects of BSJP alone, sorafenib alone, and their combination on the expression of caspase-3, caspase-9, and Bcl-2. RESULTS: BSJP decreased the survival rate of HCC cell lines, and the combination of BSJP and sorafenib further decreased the survival rate. BSJP significantly promoted cell apoptosis and blocked cell-cycle progression in HCCLM3, HepG2, and SMMC-7721 cells in a dose-dependent manner. Furthermore, the administration of BSJP and sorafenib inhibited the growth of HCCLM3 cell xenografts in nude mice, with no reduction in body weight. In vivo and in vitro experiments showed that BSJP combined with sorafenib could significantly decrease the expression of Bcl-2. CONCLUSION: Our findings suggest that the herbal formula of BSJP is a potential HCC antitumor agent.

Molecular Mechanism of Bushen Jianpi Inhibition of Postoperative Recurrence and Metastasis of Hepatocellular Carcinoma.

Compared with western medicine, traditional Chinese medicine can better regulate the internal environment and inhibit liver cancer recurrence and metastasis. Bushen Jianpi Recipe (BSJPR) is a traditional Chinese medicine for tonifying the kidney and invigorating the spleen. It has also been used to treat tumors and other related diseases. Here we explore the efficacy of BSJPR inhibition of hepatocellular carcinoma (HCC) in vivo and in vitro . We hypothesize that BSJPR reduces intrahepatic cholestasis and inflammation and increases expression of the bile acid receptor and downstream targets. This study aims to test this hypothesis and determine whether the inhibitory effect of BSJPR on liver cancer recurrence and metastasis is related to bile acid metabolism. We also observed changes in immune cell expression, suggesting that regulation of the immune microenvironment could inhibit the recurrence and metastasis of HCC. These findings provide a basis for the treatment of HCC and new ideas for follow-up studies of BSJPR.

The complete chloroplast genome of Cuscuta australis R. Br. (Convolvulaceae) and its phylogenetic implication.

The genus Cuscuta (Convolvulaceae) is an annual parasitic twining herb. There are about 200 species in this genus, which are widely distributed in tropical and subtropical areas. Cuscuta is mainly parasitic on crops bringing significant losses to the production of agriculture. Furthermore, dried seeds of C. chinensis and C. australis are used as a Chinese traditional herbal medicine. Despite the importance of Cuscuta species, it is difficult to distinguish these plants by the naked eye. Moreover, plastid sequence information available for Cuscuta species is limited. In this study, the complete chloroplast (cp) genome sequence of C. australis was determined using next-generation sequencing. The entire cp genome was determined to be 85,263 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 50,384 and 6727 bp, respectively, which were separated by a pair of 14,076 bp inverted repeat (IR) regions. The genome contained 98 genes, including 61 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. The overall GC content of the genome is 37.8%. A phylogenetic tree reconstructed by 26 chloroplast genomes reveals that C. australis is most related with Cuscuta pentagona in Convolvulaceae, with bootstrap support values of 100%.

Polygalae Radix: A review of its traditional uses, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

Polygalae Radix (Polygalaceae), the dried root of Polygala tenuifolia Willd. and Polygala sibirica L., has been widely used as a medicine for improving cognitive function. In China, Polygalae Radix has been widely used in the treatment of insomnia, forgetfulness, depression, cough, palpitation, and other diseases. More than 140 compounds have been isolated from Polygalae Radix, including saponins, xanthones, oligosaccharide esters, and so on. The compounds and extracts isolated from Polygalae Radix possess wide-ranging pharmacological activities, such as neuroprotective, antidepressant, hypnotic-sedative, anti-inflammatory, antiviral, antitumor, antioxidant, antiaging, and antiarrhythmic effects, among others. The clinical practice of traditional Chinese medicine has proved that raw Polygalae Radix can irritate the throat. Modern studies have found that raw Polygalae Radix exhibits a certain degree of toxicity to the gastrointestinal tract after long-term use or excessive doses and that its main toxic components are saponins. Thus, Polygalae Radix is usually processed, and/or combined with other herbs to reduce gastrointestinal irritation. This review investigated the pharmacokinetics of Polygalae Radix. Future research perspectives and the existing problems of Polygalae Radix were also discussed. This review can broaden the understanding regarding Polygalae Radix and provide references for further research.