[Effects of moxibustion on serum levels of ß-EP, SP and expression of IL-1ß and COX-2 protein in brainstem in rats with migraine].

OBJECTIVE: To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of ß-endorphin (ß-EP), substance P (SP) and expression of interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine. METHODS: Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of ß-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1ß in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem. RESULTS: Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of ß-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of ß-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of ß-EP was increased and COX-2 protein expression was decreased (P<0.05). CONCLUSION: Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1ß and COX-2 protein expression in brainstem, and increase the serum level of ß-EP, and the optimal effect is observed in the PT group.

Effectiveness and Safety of Chinese Medicine at Shenque (CV 8) for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD. OBJECTIVE: To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM). METHODS: China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I2=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I2=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I2=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall. CONCLUSIONS: Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).

An exploratory study on TCM syndrome differentiation in preoperative patients with colorectal cancer assisted by laboratory indicators.

Objective: This paper aims to explore the relationship between the syndrome differentiation of traditional Chinese medicine (TCM) in colorectal cancer and the clinical laboratory indicators of patients, and to further seek the laboratory indicators to assist TCM syndrome differentiation. Methods: From May 2020 to June 2021, 122 colorectal cancer patients with a clear pathological diagnosis who had not undergone surgery or chemotherapy were classified according to the TCM syndrome classification. The clinical laboratory indicators of 122 patients with preoperative colorectal cancer were collected, and the correlation between preoperative colorectal cancer TCM syndromes and Karnofsky score and clinical laboratory indicators was analyzed. The indicators affecting TCM syndromes were included in the disordered multivariate logistic regression analysis model to analyze the relative risk of the influencing factors. Results: The syndromes of colorectal cancer patients were classified into excess syndrome, deficiency syndrome, and syndrome of intermingled deficiency & excess. The differences in total bilirubin (TBIL), hemoglobin (HB), uric acid (UA), and hematocrit (HCT) between the three groups were statistically significant (P < 0.05). The indexes such as TBIL, HB, UA, and HCT in preoperative patients with excess syndrome of colorectal cancer were higher than those in patients with syndrome of intermingled deficiency & excess and deficiency syndrome, and the comparison between groups using the LSD method showed that UA and HCT were different between the excess syndrome and deficiency syndrome groups (P < 0.05). Multivariate logistic regression analysis indicated that Gender, Tumor location, TNM stage, Total protein (TP), Red blood cell (RBC), HB, HCT, Platelet (PLT) and Fibrinogen (FIB) were all risk factors affecting TCM syndromes of preoperative colorectal cancer (P < 0.05). Conclusion: There is a correlation between the TCM syndromes of colorectal cancer and the clinical laboratory indicators of the patients. Gender, Tumor location, TNM stage, TP, RBC, HB, HCT, PLT and FIB are the risk factors of TCM syndrome differentiation in preoperative patients with colorectal cancer. TBIL, UA, HB, and HCT may be the four relevant indicators of TCM syndrome differentiation in colorectal cancer.

Efficacy and Safety of Xiaoyao Recipe in the Treatment of Poststroke Depression: A Systematic Review and Meta-Analysis.

Background: Poststroke depression (PSD) is a common neuropsychiatric disorder that affects the disability, mortality, functional recovery, and quality of daily life of patients. Xiaoyao Recipe (XYR) is often used to treat PSD and has achieved good clinical effects, but it lacks reliable evidence. Objective: This study aims to evaluate the effectiveness and safety of XYR on PSD through meta-analysis. Methods: A comprehensive literature search was carried out in multiple databases, including PubMed, the Cochrane Library, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and ClinicalTrials, from inception to July 1, 2021, to collect randomized controlled trials that applied XYR for patients with PSD. For a controlled trial, the search time limit was set from the time of the database's establishment to July 2021. Two experienced researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data, evaluated the quality of the literature, and used RevMan 5.3 software for meta-analysis. Results: A total of 12 studies were included in this study, involving 882 patients with PSD who were hospitalized or outpatients. The meta-analysis results showed that the total effective rate (p < 0.00001) of the test group (XYR or XYR combined with antidepressants) after treatment was high; Hamilton's Depression Scale score (p < 0.000001), Scandinavian Stroke Scale score (p=0.004 < 0.05), and Barthel index (p < 0.00001) were improved; the incidence of adverse reactions (p < 0.00001) was low; and the serum serotonin content (p < 0.00001) was high. Conclusion: Compared with antidepressant drugs, XYR is more effective and safer in the treatment of PSD patients. However, more high-quality studies are needed to further support the above conclusions.

Shenlian (SL) Decoction, a Traditional Chinese Medicine Compound, May Ameliorate Blood Glucose via Mediating the Gut Microbiota in db/db Mice.

Shenlian (SL) decoction is a herbal formula composed of Coptis and ginseng, of which berberine and ginsenoside are the main constituents. Even though SL decoction is widely used in treating diabetes in China, the mechanism of its antidiabetes function still needs further study. Gut microbiota disorder is one of the important factors that cause diabetes. To explore the effect of SL decoction on intestinal microbiota, gut microbiota of mice was analyzed by sequencing the gut bacterial 16S rRNA V3+V4 region and metagenomics. In this study, results demonstrated that SL decoction had a better hypoglycemic effect and ß cell protection effect than either ginseng or Coptis chinensis. Alpha diversity analysis showed that all interventions with ginseng, Coptis, and SL decoction could reverse the increased diversity and richness of gut microbiota in db/db mice. PCoA analysis showed oral SL decoction significantly alters gut microbiota composition in db/db mice. 395 OTUs showed significant differences after SL treatment, of which 37 OTUs enriched by SL decoction showed a significant negative correlation with FBG, and 204 OTUs decreased by SL decoction showed a significant positive correlation with FBG. Results of KEGG analysis and metagenomic sequencing showed that SL decoction could reduce the Prevotellaceae, Rikenellaceae, and Helicobacteraceae, which were related to lipopolysaccharide biosynthesis, riboflavin metabolism, and peroxisome, respectively. It could also upregulate the abundance of Bacteroidaceae, which contributed to the metabolism of starch and sucrose as well as pentose-glucuronate interconversions. In the species level, SL decoction significantly upregulates the relative abundance of Bacteroides_acidifaciens which showed a significant negative correlation with FBG and was reported to be a potential agent for modulating metabolic disorders such as diabetes and obesity. In conclusion, SL decoction was effective in hypoglycemia and its mechanism may be related to regulating gut microbiota via upregulating Bacteroides_acidifaciens.

Xingnao Jieyu Decoction Reduces Neuroinflammation through the NF-κB Pathway to Improve Poststroke Depression.

The neuroinflammatory pathway regulated by nuclear factor kappa-B (NF-κB) plays an important role in the occurrence, development, and prognosis of poststroke depression (PSD). The regulatory effect of the traditional Chinese medicine compound Xingnao Jieyu decoction (XNJY) on the NF-κB pathway of PSD is still unclear. This study aimed to observe the effect of XNJY on PSD and explore the molecular mechanism of its intervention in the NF-κB pathway. Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress were used to establish a PSD rat model. Body mass measurement, behavioral testing, Nissl staining, ELISA, and Western blot were also performed. XNJY and fluoxetine hydrochloride (Flu) treatment of PSD model rats showed significant antidepressant effects. XNJY and Flu treatment could reduce cortical and hippocampal neuronal damage. XNJY reduced inflammation and restored the levels of IL-4, IL-10, and BDNF. In addition, XNJY showed a significant regulatory effect on the NF-κB pathway and the expression of synapse-related proteins PSD-95 and SYN. These results showed that XNJY could significantly reduce the depressive symptoms of PSD rats, and this reduction may be related to the regulation of the NF-κB signaling pathway to improve neuroinflammation and synaptic function.

Effects of dietary supplementation with glutamine on the lymphocyte proliferation and intestinal immune gene expression in broiler chickens infected with Salmonella Enteritidis.

An experiment was conducted to investigate the effects of glutamine (Gln) on the lymphocyte proliferation and intestinal immune relevant gene expression in broilers infected with Salmonella Enteritidis. 240 1-day-old broilers were divided randomly into four groups in a completely randomized design, each of which had 6 replicates. Birds were reared in battery cages for 21 days. The experimental groups were as follows: control group (unchallenged group, CON), basal diet; Salmonella Enteritidis challenged group (challenged with 2.0 × 104 CFU/mL of Salmonella Enteritidis, SCC), basal diet; Gln 1, basal diet plus Salmonella Enteritidis challenged plus Gln at 0.5% diet; Gln 2, basal diet plus Salmonella Enteritidis challenged plus Gln at 1.0% diet. The results showed that Salmonella Enteritidis infection led to some decrease in the relative weight of spleen and bursa (except at 21 d), lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and increased the heterophil percentage, H/L ratio, mRNA expression levels of TNF-α, NF-κB p65, IL-1ß, IL-6, and IL-8 in the jejunal and ileal mucosa compared with the measurements of these parameters in the CON group at d 4, 7, 14, and 21 (p < 0.05). On the other hand, chickens fed the Gln showed improved the relative weight of spleen and bursa, increased the lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and decreased the heterophil percentage, H/L ratio, and immune relevant gene expression in the jejunal and ileal mucosa compared with the measurements of these parameters in the SCC group (p < 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of Salmonella Enteritidis infection, and increase the intestinal immune barrier function of broilers.

Immunogenic exosome-encapsulated black phosphorus nanoparticles as an effective anticancer photo-nanovaccine.

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

Eradication of tumor growth by delivering novel photothermal selenium-coated tellurium nanoheterojunctions.

Two-dimensional nanomaterial-based photothermal therapy (PTT) is currently under intensive investigation as a promising approach toward curative cancer treatment. However, high toxicity, moderate efficacy, and low uniformity in shape remain critical unresolved issues that hamper their clinical application. Thus, there is an urgent need for developing versatile nanomaterials to meet clinical expectations. To achieve this goal, we developed a stable, highly uniform in size, and nontoxic nanomaterials made of tellurium-selenium (TeSe)-based lateral heterojunction. Systemic delivery of TeSe nanoparticles in mice showed highly specific accumulation in tumors relative to other healthy tissues. Upon exposure to light, TeSe nanoparticles nearly completely eradicated lung cancer and hepatocellular carcinoma in preclinical models. Consistent with tumor suppression, PTT altered the tumor microenvironment and induced immense cancer cell apoptosis. Together, our findings demonstrate an exciting and promising PTT-based approach for cancer eradication.

Antidepressant effect of Xingnao Jieyu decoction mediated by alleviating neuroinflammation in a rat model of post-stroke depression.

OBJECTIVE: To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism. METHODS: We established a rat PSD model by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Healthy SD rats were randomly divided into six groups: sham, PSD, fluoxetine (Flu), and XNJY groups at low, middle, and high doses. The sham group underwent sham operation, while the other groups underwent MCAO+CUMS. The Flu and XNJY decoction groups were intragastrically administered with Flu or different doses of XNJY for 21 consecutive days. Histopathological changes in the cortex and hippocampus were observed by staining with hematoxylin and eosin and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling. Iba1 positive cells were evaluated by immunofluorescence assay. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the cortex and hippocampus were measured by enzyme linked immunosorbent assay. RESULTS: The PSD group rats had a significant decrease in body weight, consumption of sucrose water, and locomotor activity but an increase in immobility time during a forced swimming test (P < 0.01) compared with sham group. Flu and different doses of XNJY significantly recovered these indices (P < 0.01). XNJY also inhibited neuronal damage and apoptosis in the cortex induced by PSD (P < 0.01). Furthermore, XNJY reduced the number of Iba1 positive cells and the expressions of TNF-α, IL-6, and IL-1ß, in addition to recovered the levels of 5-HT and NE in the cortex and hippocampus (P < 0.01). CONCLUSION: The alleviation of neuroinflammation might be an important mechanism of the XNJY decoction against PSD. Thus, XNJY might be a promising candidate for the treatment of PSD.

Xingnao Jieyu Decoction Ameliorates Poststroke Depression through the BDNF/ERK/CREB Pathway in Rats.

Background. The neurotrophic pathway regulated by the brain-derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear. Objective. This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway. Methods. After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive-like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5-HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p-ERK/ERK, and p-CREB/CREB in the cortical and hippocampal regions were tested by Western blot. Results. The depressive-like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5-HT, NE, and BDNF and recovered the protein levels of p-ERK/ERK, p-CREB/CREB, and BDNF in the cortical and hippocampal regions. Conclusion. These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.

Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising Photothermal Agents for Effective Cancer Therapy.

Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short-term therapeutic and inhomogeneous photothermal effect. Development of BP-based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP-polymer-based photothermal agents in the form of hydrogels for biomedical-related clinic applications.

Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

Identification and cytochemical immunolocalization of acetyl-CoA acetyltransferase involved in the terpenoid mevalonate pathway in Euphorbia helioscopia laticifers.

BACKGROUND: Terpenoids, the largest class of natural products in the plant kingdom, have been widely used in medicine. The precursors of terpenoids, isoprene phosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), were synthesized from a mevalonate (MVA) pathway and a 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway respectively. The acetyl-CoA acetyltransferase (AACT) is the initial enzyme in MVA pathway and is considered presently to be essential for terpenoid backbone biosynthesis. The basic research on cytochemistry of terpenoid metabolic enzymes is important for understanding the mechanisms underlying major metabolic processes. However, compartmentalization of AACT in plants is in controversy. Euphorbia helioscopia L. containing laticifers in the whole plant is a famous ancient folk medicine for tumor treatment, and the terpenoid is an active ingredient. Furthermore, the laticifer cell is the main synthesizing and storing site for terpenoids. RESULTS: The gene of AACT was cloned successfully from E. helioscopia, and named as EhAACT. The EhAACT expression has no significant difference among roots, stems and leaves. However, compared with the roots and stems, the EhAACT expression level is slightly higher in leaves. In addition, EhAACT recombinant protein was expressed by procaryotic expression system and anti-EhAACT antibody was prepared, the molecular weight is about 43 kDa. Western blotting results illustrated that the EhAACT antibodies specifically recognized the endogenous proteins in E. helioscopia laticifers. At last, the subcellular localization of EhAACT in E. helioscopia laticifers was observed by using colloidal gold immune-electron microscopy. EhAACT was found to mainly distribute in the endoplasmic reticulum (ER), vacuoles originated from ER and cytosol aound vacuoles originated from ER. CONCLUSIONS: As a result, we speculated that in E. helioscopia laticifers, EhAACT located in cytosol would be transferred to small vacuoles dilated from ER, and the precursors of terpenoids were synthesized in these small vacuoles, then terpenoids were further synthesized into latex particles. This result would provide theoretical basis for regulating and controlling of terpenoid biosynthesis in laticifers.