Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance.

Pathological pain, a multifaceted and debilitating ailment originating from injury or post-injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti-inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF-κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage-gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.

Phosphorus fertiliser application mitigates the negative effects of microplastic on soil microbes and rice growth.

Soil microplastics (MPs) have attracted widespread attention recently. Most studies have explored how soil MPs affect the soil's physicochemical parameters, matter circulation, and soil microbial community assembly. Similarly, a key concern in agricultural development has been the use of phosphorus (P) fertiliser, which is essential for plant health and development. However, the relationship between MPs and phosphate fertilisers and their effects on the soil environment and plant growth remains elusive. This study assessed the influence of adding low-density polyethylene MPs (1%) with different phosphate fertiliser application rates on microbial communities and rice biomass. Our results showed that MPs changed the structure of soil bacterial and phoD-harbouring microbial communities in the treatment with P fertiliser at the same level and suppressed the interactions of phoD-harbouring microorganisms. In addition, we found that MPs contamination inhibited rice growth; however, the inclusion of P fertiliser in MP-contaminated soils reduced the inhibitory action of MPs on rice growth, probably because the presence with P fertiliser promoted the uptake of NO3--N by rice in MP-contaminated soils. Our results provide further insights into guiding agricultural production, improving agricultural management, and rationally applying phosphate fertilisers in the context of widespread MPs pollution and global P resource constraints.

Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 µmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.

Multifunctional AuPt Nanoparticles for Synergistic Photothermal and Radiation Therapy.

Background: Photothermal therapy (PTT) has gained considerable interest as an emerging modality for cancer treatment in recent years. Radiation therapy (RT) has been widely used in the clinic as a traditional treatment method. However, RT and PTT treatments are limited by side effects and penetration depth, respectively. In addition, hypoxia within the tumor can lead to increased resistance to treatment. Methods: We synthesized multiple sizes of AuPt by modulating the reaction conditions. The smallest size of AuPt was selected and modified with folic acid (FA) for PTT and RT synergy therapy. Various methods including transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FITR) are used to determine the structure and composition of AuPt-FA (AF). In addition, we researched the photothermal properties of AF with IR cameras and infrared lasers. Flow cytometry, colony formation assays, CCK8, and fluorescent staining for probing the treatment effect in vitro. Also, we explored the targeting of AF by TEM and In Vivo Imaging Systems (IVIS). In vivo experiments, we record changes in tumor volume and weight as well as staining of tumor sections (ROS, Ki67, and hematoxylin and eosin). Results: The AuPt with particle size of 16 nm endows it with remarkably high photothermal conversion efficiency (46.84%) and catalase activity compared to other sizes of AuPt (30 nm and 100 nm). AF alleviates hypoxia in the tumor microenvironment, leading to the production of more reactive oxygen species (ROS) during the treatment. In addition, the therapeutic effect was significantly enhanced by combining RT and PTT, with an apoptosis rate of 81.1% in vitro and an in vivo tumor volume reduction rate of 94.0% in vivo. Conclusion: These results demonstrate that AF potentiates the synergistic effect of PTT and RT and has the potential for clinical translation.

Identification of glycogen phosphorylase L as a potential target for lung cancer.

Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.

Indirubin-3'-oxime promotes the efficacy of GnRHa in obese-induced central precocious puberty and maintains normal bone growth and body weight via the ERK-Sp1-KISS-1/GPR54 axis.

Central precocious puberty (CPP) is a widespread developmental abnormality. The application of gonadotrophin-releasing hormone agonist (GnRHa) is widely useful for the medical therapy of CPP. This study aimed to investigate the combination effect and mechanism of indirubin-3'-oxime (I3O), an active ingredient analogue of traditional Chinese medicine, and GnRHa treatment on the progression of CPP. First, female C57BL/6 mice were fed with a high-fat diet (HFD) for the induction of precocious puberty and treated with GnRHa and I3O alone or in combination. Development of sexual maturation, bone growth and obesity were determined by vaginal opening detection, H&E staining and ELISA. The protein and mRNA expression levels of related genes were evaluated via western blotting, immunohistochemical method and RT-qPCR. Subsequently, tBHQ, an inhibitor of ERK, was applied to verify whether the mechanism of I3O was associated with this signaling. The results showed that the treatment of I3O alone or in combination with GnRHa could alleviate the HFD-induced earlier vaginal opening and serum levels of the gonadal hormone in mice. And, I3O could significantly eliminate the role of growth deceleration of GnRHa in bone development and reversed the side effect of GnRHa on body weight. More importantly, we found that I3O decreased the expression of KISS-1 and GPR54 by suppressing the phosphorylation of ERK1/2 and Sp1 in the hypothalamus in mice. In summary, these data indicated that I3O could promote the efficacy of GnRHa in HFD-induced precocious puberty, and maintain bone growth and body weight in mice via the ERK-Sp1-KISS-1/GPR54 axis.

Performance and mechanism of phosphorus adsorption removal from wastewater by a Ce-Zr-Al composite adsorbent.

With the increasingly serious eutrophication of global water bodies and the strict discharge standards of tail water in wastewater treatment plants (WWTPs), there is an urgent technology need for efficient deep phosphorus removal from wastewater. A composite cerium-based adsorbent (Ce-Zr-Al) was synthesized by coprecipitation method for the adsorption of low concentration phosphorus in water. The performance of the Ce-Zr-Al composite adsorbent was explored, and the mechanism was also revealed through the analyses including SEM, BET, XPS, and FT-IR. The results showed that the composite adsorbent had excellent phosphorus removal performance. The phosphorus removal rate reached up to 92.6%, and the phosphorus concentration in effluent was less than 0.074 mg/L. The phosphate adsorption capacity of saturation was 73.51 mg/g. The adsorption process of phosphate was in accordance with pseudo-second-order kinetic model and Langmuir model. In addition, the composite adsorbent had a high zero potential point (pH PZC= 8) and a wide range of pH application. After the repeated desorption for 10 times in NaOH solution, the composite adsorbent still maintained good adsorbability (adsorption rate > 94%). The ligand exchange and electrostatic adsorption played the main role for the phosphorus removal from water using the composite adsorbent.

[Quality evaluation and multi-spectral identification of origin herbs of Lonicerae Japonicae Flos based on grey correlation-TOPSIS method].

The grey correlation-TOPSIS method was used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos, and the Fourier transform near-infrared(NIR) and mid-infrared(MIR) spectroscopy was applied to establish the identification model of origin herbs of Lonicerae Japonicae Flos by combining chemometrics and spectral fusion strategies. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, secoxyloganin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C in six origin herbs of Lonicerae Japonicae Flos was determined by high-performance liquid chromatography(HPLC), and their quality was evaluated by the grey correlation-TOPSIS method. The Fourier transform NIR and MIR spectra of six origin herbs of Lonicerae Japonicae Flos(Lonicera japonica, L. macranthoides, L. hypoglauca, L. fulvotomentosa, L. confuse, and L. similis) were collected. At the same time, principal component analysis(PCA), support vector machine(SVM), and spectral data fusion technology were combined to determine the optimal identification method for the origin herbs of Lonicerae Japonicae Flos. There were differences in the quality of the origin herbs of Lonicerae Japonicae Flos. Specifically, there were significant differences between L. japonica and the other five origin herbs(P<0.01). The quality of L. similis was significantly different from that of L. fulvotomentosa, L. macranthoides, and L. hypoglauca(P=0.008, 0.027, 0.01), and there were also significant differences in the quality of L. hypoglauca and L. confuse(P=0.001). The PCA and SVM 2D models based on a single spectrum could not be used for the effective identification of the origin herbs of Lonicerae Japonicae Flos. The data fusion combined with the SVM model further improved the identification accuracy, and the identification accuracy of the mid-level data fusion reached 100%. Therefore, the grey correlation-TOPSIS method can be used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos. Based on the infrared spectral data fusion strategy and SVM chemometric model, it can accurately identify the origin herbs of Lonicerae Japonicae Flos, which can provide a new method for the origin identification of medicinal materials of Lonicerae Japonicae Flos.

Dysosmaflavonoid A-F, new flavonols with potent DPPH radical scavenging activity from Dysosma versipellis.

Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 µM, respectively, in comparison with Trolox (IC50, 15.80 µM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect.

Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults / 中国中药杂志

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Reflection on the Changes in the Scope of Ethical Review / 中国医学伦理学

At the end of February 2023, the new Notice on the Issuance of Ethical Review Measures for Life Science and Medical Research Involving Humans was issued by the National Health Commission, the Ministry of Education, the Ministry of Science and Technology, and the State Administration of Traditional Chinese Medicine. It adheres to the basic principles and institutional framework of the Ethical Review Measures for Biomedical Research Involving Humans , and combines with the actual situation of domestic ethical work to optimize and improve the details and procedures of the review. Based on the Ethical Review Measures for Biomedical Research Involving Humans, the Ethical Review Measures for Life Science and Medical Research Involving Humans have expanded the scope of application of ethical review. Different experts in the field have discussed in detail the changes in the scope of review, and proposed review procedures that may need to be corresponding adjustments based on the changes for the readers’ reference.

Role of potential bioactive metabolites from traditional Chinese medicine for type 2 diabetes mellitus: An overview.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR). The number of diabetic patients globally has been rising over the past decades. Although significant progress has been made in treating diabetes mellitus (DM), existing clinical drugs for diabetes can no longer fully meet patients when they face complex and huge clinical treatment needs. As a traditional and effective medical system, traditional Chinese medicine (TCM) has a unique understanding of diabetes treatment and has developed many classic and practical prescriptions targeting DM. With modern medicine and pharmacy advancements, researchers have discovered that various bioactive metabolites isolated from TCM show therapeutic on DM. Compared with existing clinical drugs, these bioactive metabolites demonstrate promising prospects for treating DM due to their excellent biocompatibility and fewer adverse reactions. Accordingly, these valuable metabolites have attracted the interest of researchers worldwide. Despite the abundance of research works and specialized-topic reviews published over the past years, there is a lack of updated and systematic reviews concerning this fast-growing field. Therefore, in this review, we summarized the bioactive metabolites derived from TCM with the potential treatment of T2DM by searching several authoritative databases such as PubMed, Web of Science, Wiley Online Library, and Springer Link. For the convenience of readers, the content is divided into four parts according to the structural characteristics of these valuable compounds (flavonoids, terpenoids, alkaloids, and others). Meanwhile, the detailed mechanism and future directions of these promising compounds curing DM are also summarized in the related sections. We hope this review inspires increasingly valuable and significant research focusing on potential bioactive metabolites from TCM to treat DM in the future.

Compact 100GBaud driverless thin-film lithium niobate modulator on a silicon substrate.

Electro-optic (EO) modulators with a high modulation bandwidth are indispensable parts of an optical interconnect system. A key requirement for an energy-efficient EO modulator is the low drive voltage, which can be provided using a standard complementary metal oxide semiconductor circuity without an amplifying driver. Thin-film lithium niobate has emerged as a new promising platform, and shown its capable of achieving driverless and high-speed EO modulators. In this paper, we report a compact high-performance modulator based on the thin-film lithium niobate platform on a silicon substrate. The periodic capacitively loaded travelling-wave electrode is employed to achieve a large modulation bandwidth and a low drive voltage, which can support a driverless single-lane 100Gbaud operation. The folded modulation section design also helps to reduce the device length by almost two thirds. The fabricated device represents a large EO bandwidth of 45GHz with a half-wave voltage of 0.7V. The driverless transmission of a 100Gbaud 4-level pulse amplitude modulation signal is demonstrated with a power consumption of 4.49fj/bit and a bit-error rate below the KP4 forward-error correction threshold of 2.4×10-4.

[Effect of Antibiotic-Degrading Bacteria on Maturity and Bacterial Community Succession During Pig Manure Composting].

The inoculation of antibiotic-degrading bacteria into manure could promote the removal of antibiotics during composting. However, knowledge on the impact of inoculating these antibiotic-degrading bacteria on the composting process and indigenous microbial community succession is still limited. This study assessed the antibiotic removal efficiency in pig manure after inoculating a microbial inoculum with antibiotic-degrading bacteria as the key component. The effect of inoculating this microbial inoculum on the physicochemical dynamics and the succession of the manure bacterial community during composting was also analyzed. The results showed that the antibiotic degradation in pig manure reached 81.95% after inoculating the microbial inoculum. When compared with that in the control, the total concentration of antibiotic residues in manure with the microbial agent inoculated was decreased by 42.18%. During composting, inoculating the microbial inoculum accelerated the temperature rise of compost, favored water loss, and alleviated the release of NH3 and H2S. Moreover, the total nutrient content (nitrogen, phosphorus, and potassium) in the final compost and the germination index of radish seeds increased by 6.80% and 68.33%, respectively, after inoculating this microbial inoculum. Furthermore, inoculating the microbial inoculum increased the content of stable organic carbon in the final compost and decreased the content of recalcitrant substances such as cellulose and hemicellulose. The analysis of the manure bacterial community showed that inoculating the microbial inoculum increased the relative abundances of Actinomycetes and Firmicutes in the compost. In particular, the thermophilic bacteria that was positively related to the compost temperature was increased significantly (P<0.01) after inoculating the microbial inoculum, whereas the relative abundance of pathogenic bacteria was correspondingly decreased. Network analysis of the bacterial coexistence pattern showed that inoculating this microbial inoculum also changed the interaction pattern of indigenous manure bacterial communities, which greatly reduced the complexity and connectivity of the bacterial interaction and improved the ecological relationship between beneficial bacteria and other bacterial communities. The effect of this microbial inoculum on the interaction with manure bacterial community laid a foundation for the establishment of a new and healthier composting bacterial community. This study provides a scientific basis for the application and development of multifunctional antibiotic-degrading microbial agents in manure treatments.

A localization method for guide pin insertion points in the treatment of femoral neck fracture with closed reduction and percutaneous cannulated screw fixation.

Background: Closed reduction and percutaneous cannulated screw fixation is the preferred surgical method for treating femoral neck fractures in elderly patients under 70 years old. The key to the operation is the precise insertion of the guide pin after the successful reduction. However, there is no universally accepted standard for the localization of the guide pin insertion point. This study introduces our invention of a localization method for guide pin insertion points. Methods: We used fluoroscopic frequency, operative time, union rates, and complications to retrospectively evaluate the treatment and outcome of femoral neck fractures using our localization method for guide pin insertion points. The study included ten patients treated at Affiliated Hospital of Shandong University of Traditional Chinese Medicine between 2010 and 2014 for femoral neck fracture using our localization method for guide pin insertion points. Results: Our results showed that the mean number of fluoroscopies was 5 (range, 4-8), and the mean operative time was 32 minutes (range, 25-51 minutes). All 10 patients achieved union at an average of 3.4 months (range, 2.8-6.2 months) without complications after the operation. The average follow-up time was 13.2 months (range, 12.2-16 months). The treatment of femoral neck fracture with our localization method for guide pin insertion points resulted in satisfactory curative efficacy without complications. Conclusions: Our localization method offers distinct advantages, including the accuracy and simplicity of the operation, a low rate of complications, and adequate biomechanical stability. As such, it provides a feasible method for clinical treatment.

Efficacy and Safety of Transcutaneous Electrical Acupoint Stimulation for Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials.

Objective: This meta-analysis aims to evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) in treating post-operative pain. Methods: This meta-analysis was registered in PROSPERO (CRD42021286753). We searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials (RCTs) about TEAS in treating postoperative pain that were published before November 2021. The primary outcome was visual analogue scale (VAS) within 24 h after surgery. The secondary outcomes included postoperative opioid analgesic drug consumption and the occurrence of adverse reactions within the postoperative 24-72 h. Adverse reactions included dizziness, nausea, and vomiting. Continuous variables were analyzed using mean difference (MDs) or standardized mean difference (SMDs) and 95% CIs. Relative risk (RR) and 95% CI were used for dichotomous data. The data were pooled and analyzed by RevMan 5.4 and STATA15.0 software. Results: Seventeen trials with 1375 participants were included. The current results suggested that application of TEAS showed obvious superiority in reducing VAS scores (SMD = -1.51, 95% CI = -2.20∼-0.82, I2 = 96%). Subgroup analysis was performed according to open surgery and minimally invasive surgery. VAS scores were decreased after surgery at 24 h (SMD = -0.84, 95% CI = -1.07∼-0.6, I2 = 96%; SMD = -0.88, 95% CI = -1.02∼-0.75, I2 = 96%). The incidence of postoperative dizziness and nausea and vomiting was significantly lower in the TEAS group within postoperative 24-72 h (RR = 0.48, 95% CI = 0.34∼0.68, I2 = 0%; RR = 0.66, 95% CI = 0.44∼1.01, I2 = 69%; and RR = 0.49, 95% CI = 0.24∼1.00, I2 = 51%). Postoperative opioid analgesics were also reduced in the TEAS group within 72 h after surgery (SMD = -2.10, 95% CI = -3.37∼-0.82, I2 = 96%). Conclusions: TEAS can reduce postoperative pain as well as the incidence of dizziness, nausea, and vomiting and the number of analgesics used after surgery. TEAS is a reasonable modality to incorporate into a multimodal management approach for postoperative pain.

Quality of Evidence Supporting the Role of Curcuma Longa Extract/Curcumin for the Treatment of Osteoarthritis: An Overview of Systematic Reviews.

Background: Well known for its good anti-inflammatory effect, curcuma longa extract (CLE)/curcumin (C) has a potential effect on osteoarthritis (OA), and a large number of researchers have completed several systematic reviews/meta-analyses (SRs/MAs) in this research area. However, the methodological and evidentiary quality of these SRs/MAs need to be further evaluated, and whether these findings provide reliable evidence for clinicians remains controversial. Methods: Two researchers collected data from seven databases for SRs/MAs that are about randomized controlled trials (RCTs) on CLE/C for OA. Assessment was made for the SRs/MAs included in this article by means of the Assessment System for Evaluating Methodological Quality 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Nine published SRs/MAs were included in our study. According to the results of the AMSTAR-2 assessment, only one SR/MA was assessed as high quality. According to the ROBIS evaluation results, only 2 SRs/MAs have a low risk of bias. According to the results of the PRISMA checklist assessment, only 2 SRs/MAs studies fully reported the checklist, while other studies had reporting flaws. According to GRADE, a total of 59 effect sizes extracted from the included SRs/MAs were evaluated, among which no effect size was rated as high. Conclusions: CLE/C may be an effective and safe complementary treatment for OA. However, further standard SRs/MAs and RCTs are needed to provide an evidence-based medical rationale for this.

Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells.

Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.

Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and in vitro Studies.

BACKGROUND: Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. METHODS: By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. RESULTS: Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis- free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. CONCLUSION: AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.