The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

The potential for traditional Chinese therapy in treating sleep disorders caused by COVID-19 through the cholinergic anti-inflammatory pathway.

Since the outbreak of Coronavirus disease (COVID-19) in 2019, it has spread rapidly across the globe. Sleep disorders caused by COVID-19 have become a major concern for COVID-19 patients and recovered patients. So far, there's no effective therapy on this. Traditional Chinese therapy (TCT) has a great effect on sleep disorders, with rare side effects and no obvious withdrawal symptoms. The cholinergic anti-inflammatory pathway, a neuroregulatory pathway in the central nervous system that uses cholinergic neurons and neurotransmitters to suppress inflammatory responses, has been reported to be associated with sleep disorders and psychiatric symptoms. Many studies have shown that TCT activates the cholinergic anti-inflammatory pathway (CAP), inhibits inflammation, and relieves associated symptoms. Therefore, we believe that TCT may be a potential therapeutic strategy to alleviate sleep disorders induced by COVID-19 through CAP. In this review, we analyzed the relationship between cytokine storm induced by Coronavirus and sleep disorders, explained the influence of CAP on sleep disorders, discussed the TCT's effect on CAP, and summarized the treatment effect of TCT on sleep disorders. Based on these practical researches and theoretical basis, we propose potential strategies to effectively improve the sleep disorders caused by COVID-19.

Systematic review and meta-analysis of acupuncture in the treatment of cognitive impairment after stroke.

BACKGROUND: We aim to make a systematic evaluation of the clinical efficacy of acupuncture in the treatment of cognitive impairment after stroke, to provide evidence-based medical evidence for clinical practice. METHODS: We searched all the randomized controlled trials of China National Knowledge Infrastructure, Wan fang data knowledge service platform, VIP Chinese periodical service platform full-text Journal Database, Chinese Biomedical Literature Database, Cochrane Library Database, and PubMed Database about acupuncture treatment of post-stroke cognitive impairment (PSCI). Two researchers independently screened the literature and extracted the data according to the inclusion and exclusion criteria. The bias risk assessment manual of Cochrane collaboration Network was used to evaluate the bias risk, and all data were analyzed by Stata16.0. RESULTS: Fourteen articles were included, with a total of 2402 patients. Meta-analysis showed that acupuncture combined with routine therapy could significantly reduce the score of cognitive impairment symptoms compared with the control group. The mini-mental state examination scale (MMSE) score (weighted mean difference [WMD] = 3.23, 95% confidence interval [CI]: 1.89-4.56, P < .01), Montreal cognitive assessment scale (MoCA) score (WMD = 3.41, 95% CI: 0.93-5.89, P < .01), Barthel index of activities of daily living (MBI) score (WMD = 4.59, 95% CI: 1.43-7.75, P < .01), and Lowenstein assessment scale (LOTCA) score (WMD = 8.60, 95% CI: 6.32-10.89, P = .00) were significantly improved in the patients receiving group acupuncture combined with routine therapy. CONCLUSION: Acupuncture combined with routine therapy seems to be more effective than conventional therapy alone in the treatment of PSCI. However, the differences between different acupuncture types need to be clarified in more high-quality randomized controlled trials.

Alantolactone reduced neuron injury via activating PI3K/Akt signaling pathway after subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is a common disease with high morbidity and mortality, which can cause pathological, physiological, and biological reactions. SAH causes a series of responses such as neuronal and cerebral cortex damage, which in turn leads to inflammation and apoptosis. Traditional Chinese medicine has a strong anti-inflammatory effect, such as Alantolactone (ATL). However, studies on ATL therapy for SAH have not been reported. We observed the neurological scores, brain water content, Evans blue (EB) extravasation, neuroinflammation, and apoptosis via performing an enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence staining, and other methods after SAH. In this study, we found that ATL treatment attenuated the neurologic deficits, inhibited neuronal apoptosis and inflammatory reaction, promoted polarization of microglia toward the M2 phenotype, and activated the PI3K/Akt signaling pathway. ATL can reduce the neurons and cerebral cortex damage of SAH rats through activating PI3K/Akt signaling pathway.

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1ß, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

Puerarin suppresses proliferation of endometriotic stromal cells in part via differential recruitment of nuclear receptor coregulators to estrogen receptor-α.

BACKGROUND AND OBJECTIVES: Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17ß-estradiol and producing an anti-estrogenic effect. In our early clinical practice to treat endometriosis, a better therapeutic effect was achieved if the formula of traditional Chinese medicine included Radix puerariae. This study was to investigate whether puerarin could suppress the proliferation of endometriotic stromal cells (ESCs) and to further elucidate the potential mechanism. METHODS AND RESULTS: The ESCs were successfully established. The effects of puerarin on the proliferation of ESCs, cell cycle and apoptosis were determined by Cell Counting Kit-8 assay and flow cytometry. The mRNA and protein levels of cyclin D1 and cdc25A were detected by real-time PCR and Western blot analysis. Coimmunoprecipitation was applied to examine the recruitment of nuclear receptor coregulators to the estrogen receptor-α. We found that puerarin can suppress estrogen-stimulated proliferation partly through down-regulating the transcription of cyclin D1 and cdc25A by promoting the recruitment of corepressors to estrogen receptor-α as well as limiting that of coactivators in ESCs. CONCLUSIONS: Our data suggest that puerarin could suppress the proliferation of ESCs and could be a potential therapeutic agent for the treatment of endometriosis.

[Bushen Huoxue Huayu Recipe up-regulates expression of insulin receptor substrate-1 and phosphorylation of tyrosine in adipose tissue in androgen sterilized rats].

OBJECTIVE: To investigate the expression of insulin receptor substrate-1 (IRS-1) and phosphorylation of tyrosine in androgen sterilized rats (ASRs) and the effects of Bushen Huoxue Huayu Recipe (BHHR), a compound Chinese herbal medicine for tonifying kidney and activating blood, on the ASRs, and to analyze the possible mechanism. METHODS: ASR models were established by means of testosterone injected subcutaneously at the age of 9 days. The model rats were randomly divided into BHHR group (n=15) and untreated group (n=15); the rats in normal group (n=15) were injected with oil. The rats in the BHHR group were treated with BHHR for 30 days, and the rats in model group and normal group were treated with distilled water for 30 days. Body weight and area under the curve (AUC) of insulin were measured after treatment. Expression of IRS-1 and phosphorylation of tyrosine in adipose tissue in ASRs were analysed by immunohistochemical method. RESULTS: The body weight and insulin AUC in the untreated group were increased and more than those in the BHHR group and the normal control group (P<0.05). Expression of IRS-1 and phosphorylation of tyrosine in normal group were significantly higher than those in the untreated group (P<0.05), and those in BHHR group were improved and significantly different from those in the untreated group (P<0.05). CONCLUSION: BHHR can increase the expression of IRS-1 and phosphorylation of tyrosine in adipose tissue in IR rats, which may be one of its mechanisms in improving insulin sensitivity of the target tissues.

[Effects of Bushen Huayu Qutan Recipe on local ovarian factors in androgen-sterilized rats].

OBJECTIVE: To explore the effects of Bushen Huayu Qutan Recipe (BHQR), a compound traditional Chinese herbal medicine, on local ovarian factors in androgen-sterilized rats (ASR). METHODS: One hundred and five 9-day-old SD rats were randomly divided into normal control group (15 rats) and ASR group (90 rats). ASR was induced by subcutaneous injection of testosterone propionate, and the rat model of ASR was established successfully in 30 rats in the ASR group. Thirty ASR rats were randomly divided into untreated group and BHQR-treated group. There were 15 rats in each group. The rats in BHQR-treated group were intragastrically administered with BHQR. The rats in the normal control and untreated groups were intragastrically administered with distilled water. They were all treated for 30 days. The levels of serum testosterone and insulin (INS) were measured by radioimmunoassay. The inhibin (INH) level, and the expressions of insulin-like growth factor-I(IGF-I) and vascular endothelial growth factor (VEGF) in ovary were determined by immunohistochemical method. RESULTS: None of the ASR ovulated and all the rats in the normal control group ovulated. The rate of ovulation in BHQR-treated group was 66.67%. The serum concentrations of testosterone and INS in the untreated group were significantly higher than those in the normal control group (P<0.05), and the serum concentrations of testosterone and INS in BHQR-treated group were decreased as compared with the untreated group (P<0.05). The levels of ovarian INH, IGF-I and VEGF in the untreated group were significantly higher than those in the normal control group (P<0.01), and the levels of ovarian INH, IGF-I and VEGF in BHQR-treated group were decreased as compared with the untreated group (P<0.01). CONCLUSION: BHQR is an effective recipe in promoting ovulation, and the effects of BHQR on balancing the internal environment of ovary may be due to the reduction of serum INS level and decrease in the expressions of ovarian INH, IGF-I and VEGF.