Cyclo(L-Pro-L-Trp) from Chilobrachys jingzhao alleviates formalin-induced inflammatory pain by suppressing the inflammatory response and inhibiting TRAF6-mediated MAPK and NF-κB signaling pathways.

Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.

Electroacupuncture facilitates vascular normalization by inhibiting Glyoxalase1 in endothelial cells to attenuate glycolysis and angiogenesis in triple-negative breast cancer.

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

[Exploration of the thinking and methods in treatment of cancer pain with acupuncture and moxibustion on the base of the fascia theory].

There is a commonality between jingjin (muscle region of meridian) and the fascial network for coordinating the balance in the body. The occurrence and the progression of tumor may disrupt the overall coordination between the fascial network and jingjin directly or indirectly, thereby, the impairment of this coordination may result in cancer pain. Rooted on the theory of overall balance of the fascial network, and combined with understanding of pain in jingjin theory, professor HUANG Jin-chang emphasizes the importance of "relaxing the knot" in treatment of cancer pain. It is recommended to select the fascia reaction point as the target point, in accordance with the principle of balance adjustment and apply various acupuncture and moxibustion therapies, such as Fu's subcutaneous needling, small-needle scalpel therapy, fire needling, and moxibustion.

Enantiomeric pairs of macrocyclic acylphloroglucinols from Syzygium szemaoense.

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.

Dimeric sesquiterpenoids and anti-inflammatory constituents of Sarcandra glabra.

Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells.

[Research status and trends of acupuncture and moxibustion for cancer：a bibliometric analysis based on CiteSpace and VOSviewer].

To analyze the research status of acupuncture and moxibustion for cancer at home and abroad in the past 45 years by using bibliometric and scientific knowledge map methods，and explore the development trends in future. The literature of acupuncture and moxibustion for cancer was retrieved from CNKI and Web of Science (WOS) till December 31, 2020 since the database establishment, and CiteSpace and VOSviewer software were used to perform visual map analysis through cooperation network, keyword co-occurrence, keyword timeline, keyword emergence and other methods. Totally, 1 585 literature in CNKI and 1 564 literature in WOS were included, and the annual publication amount showed a fluctuating upward trend. Cooperation between countries was centered on China and the United States, and there was relatively little cooperation among different institutions. The analysis of keyword and cited literature showed that researches focused on the control of acupuncture and moxibustion therapy on cancer complications and adverse reactions of western medicine. The main research types in WOS were systematic review and randomized controlled trial (RCT), while in CNKI was review, depth studies on mechanism of acupuncture and moxibustion for cancer were rare. The concern about the quality of life of cancer patients may become research emphasis in the field of acupuncture and moxibustion for cancer in future, and the research scope tends to integrative and holistic oncology.

Efficacy of acupuncture therapy for improving anorexia in tumor patients: a Meta-analysi.

OBJECTIVE: To use evidence-based medicine to systematically evaluate the effectiveness and safety of acupuncture therapy for improving anorexia in tumor patients. METHODS: We queried the China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, PubMed, Cochrane Library, and Embase databases to identify reports of randomized controlled trials (RCTs) that applied acupuncture therapy to improve anorexia in tumor patients, and used Rev Man 5.3 software to conduct a Meta-analysis of the effective rate, appetite score, Karnofsky Performance Status (KPS) score, Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale, and body weight in each study. Subgroup analysis was conducted based on whether radiotherapy or chemotherapy were also administered. RESULTS: A total of 10 RCTs were included with a total of 648 patients, including 343 patients in the treatment group and 305 patients in the control group. The Meta-analysis results showed that the clinical efficacy, appetite score, KPS score, and FAACT score of the treatment group (which received acupuncture to improve appetite) were better than those of the control group, and the difference was statistically significant (P < 0.05); however, there was no statistically significant difference in body weight between the treatment group and the control group (P > 0.05). The results of the subgroup analysis showed that the effective rate and appetite score for patients with long-term and chronic loss of appetite who underwent acupuncture were better than those of the control group, and the difference was statistically significant (P < 0.05). CONCLUSIONS: Acupuncture therapy has good efficacy and safety in the treatment of anorexia in tumor patients, and it also has good efficacy and safety for long-term and chronic loss of appetite. The reliability and stability of the above results need to be confirmed by high-quality RCTs with larger sample sizes.

Acylphloroglucinol derivatives with ATP citrate lyase inhibitory activities from Syzygium oblatum Wall.

Nine undescribed acylphloroglucinol derivatives, oblatones A-I, along with three known ones, were isolated from Syzygium oblatum. Their structures were determined on the basis of extensive spectroscopic analysis, including NMR and MS data interpretation. Oblatones A and B possess an alkylated chromanone scaffold featuring a hemiketal moiety. Oblatones C and D are the first acylphloroglucinol derivatives with an α,ß-unsaturated ketone lipid chain. Some of the isolates showed inhibitory effects on ATP citrate lyase in vitro. The binding mode of oblatone A was predicted by molecular docking.

[Discussion on registry study of acupuncture-moxibustion for malignant pleural effusion].

Malignant pleural effusion (MPE) is one of the common complications of tumor. Acupuncture-moxibustion therapy has several advantages for treatment of MPE. Acupuncture is regarded as a complex individualized intervention, and its characteristics of TCM is difficult to be reflected by strict randomized controlled trials. The registry study provides more possibilities for the data collection of individualized diagnosis and treatment under the guidance of the overall concept and syndrome differentiation, and is more suitable for data management and collection of large samples and multi-center trials in the real-world study. It has become an opportunity to carry out real-world study of acupuncture for MPE. There are many challenges in the registry study of acupuncture for MPE. However, it is of great significance to collect real-world data of acupuncture for MPE to improve the clinical effect of MPE and provide a new clinical research method for acupuncture in tumors and related complications.

Evaluation of Local Injection of Bevacizumab against Triple-Negative Breast Cancer Xenograft Tumors.

BACKGROUND AND OBJECTIVE: Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors. METHODS: Mice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated. RESULTS: The growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration. CONCLUSION: This study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ.

RNA interference-mediated gene silencing of cyclophilin A enhances the radiosensitivity of PAa human lung adenocarcinoma cells in vitro.

Radiotherapy is currently the major therapeutic strategy for patients with lung cancer. However, radioresistance and various side effects continue to present challenging issues for this form of treatment. A recent study demonstrated that cyclophilin A (CyPA) was overexpressed in non-small cell lung cancer and, therefore, presents a novel potential therapeutic target. In addition, gene-radiotherapy is a novel method for cancer treatment. Therefore, the objective of the present study was to investigate the potential effect of CyPA silencing on radiosensitivity in human lung adenocarcinoma in vitro. The stable CyPA-silencing lung adenocarcinoma (PAa) cell line was generated using lentivirus-mediated small hairpin RNAs. The knockdown of CyPA was determined using fluorescent microscopy and western blot analysis. Cells were irradiated using various doses of cobalt-60 (0, 2, 4, 6 and 8 Gy). The radiosensitizing effects were determined by a clonogenic survival assay. Apoptosis and cell cycle distribution were evaluated using flow cytometry. Silencing of CyPA significantly increased the apoptosis of PAa cells. In addition, the radiosensitivity of cells was markedly enhanced following CyPA silencing. Furthermore, silencing of CyPA, in combination with irradiation, induced G2/M phase cell cycle arrest. Taken together, the data suggest that the silencing of CyPA, combined with radiation therapy, may increase the therapeutic efficacy of lung cancer treatment through regulation of the cell cycle and apoptosis-associated signaling pathways.

A proteomical study on the radiosensitized target molecules of fuzheng zengxiao formula in pulmonary adenocarcinoma nude mice model.

OBJECTIVE: To investigate the radiosensitized target of Fuzheng Zengxiao Formula. METHODS: The pulmonary adenocarcinoma (PAa) nude mice of tumor transplantation model were prepared and divided into four groups: Group I (blank control group, n = 10), Group II (simple radiotherapy group, n = 10), Group III (radiotherapy plus Fuzheng Zengxiao Formula, n = 10) and Group IV (radiotherapy plus metronidazole, n = 10). Radiation of X-rays was given to the tumors in Group I, II and III when they were averagely about 1 centimetre in diameter. 23 hours later, the tumors were taken, the total proteins were extracted, and the protein contents were determined. The proteins were isolated with two dimensional gel electrophoresis, and the differentially expressed proteins were analyzed with mass spectrometry and identified by protein database. RESULTS: Six significant proteins, including apolipoprotein E, ceratin75, S100A9, cyclophilin A, S100A10 and hemoglobin, were determined. Compared with Group I, apolipoprotein E and ceratin75 highly expressed in the Group II; compared with Group II, S100A9, cyclophilin A and hemoglobin had high expression in the Group III; compared with Group II, S100A9, cyclophilin A, S100A10 and hemoglobin had high expression in the Group IV; compared with Group IV, S100A9 and S100A10 had low expression and hemoglobin had high expression in Group III. CONCLUSION: The radiosensitization of Fuzheng Zengxiao Formula is related with the improvement of hypoxia state; and possibly S100A9 and cyclophilin A are the target proteins of Fuzheng Zengxiao Formula in radiosensitization.

Clinical study of Jiawei Huangqi Guizhi Wuwu Decoction in preventing and treating peripheral neuro-sensory toxicity caused by oxaliplatin.

OBJECTIVE: To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction (JHGWD) in treating neuro-sensory toxicity induced by oxaliplatin. METHODS: A randomized controlled self-crossover trial was performed. Thirty-one patients were randomly divided into AB and BA groups. Patients in A cycle belonged to the treated group, who were treated with chemotherapy combined with oxaliplatin plus JHGWD. Patients in B cycle belonged to the control group and were treated with chemotherapy alone. The peripheral neuro-sensory toxicity was observed and analyzed. RESULTS: The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the extremities, electrified sensation, formication, foreign body sensation and pain that might be exacerbated by exposure to cold. Twenty patients (64.5%) suffered from neuro-sensory toxicity in the treated group and 27 cases (87.1%) in the control group. Symptoms were more serious and lasted longer in the control group than those in the treated group (P < 0.01). CONCLUSION: JHGWD could prevent and reduce the occurrence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin.