Low dose PFDA induces DNA damage and DNA repair inhibition by promoting nuclear cGAS accumulation in ovarian epithelial cells.

Per- and polyfluoroalkyl substances (PFAS), the versatile anthropogenic chemicals, are popular with the markets and manufactured in large quantities yearly. Accumulation of PFAS has various adverse health effects on human. Albeit certain members of PFAS were found to have genotoxicity in previous studies, the mechanisms underlying their effects on DNA damage repair remain unclear. Here, we investigated the effects of Perfluorodecanoic acid (PFDA) on DNA damage and DNA damage repair in ovarian epithelial cells through a series of in vivo and in vitro experiments. At environmentally relevant concentration, we firstly found that PFDA can cause DNA damage in primary mouse ovarian epithelial cells and IOSE-80 cells. Moreover, nuclear cGAS increased in PFDA-treated cells, which leaded to the efficiency of DNA homologous recombination (HR) decreased and DNA double-strand breaks perpetuated. In vivo experiments also verified that PFDA can induce more DNA double-strand breaks lesions and nuclear cGAS in ovarian tissue. Taken together, our results unveiled that low dose PFDA can cause deleterious effects on DNA and DNA damage repair (DDR) in ovarian epithelial cells and induce genomic instability.

Extracellular Vesicle-Packaged circATP2B4 Mediates M2 Macrophage Polarization via miR-532-3p/SREBF1 Axis to Promote Epithelial Ovarian Cancer Metastasis.

Ovarian cancer is one of the most common gynecologic malignancies with a highly immunosuppressive tumor microenvironment (TME) and poor prognosis. Circular RNA (circRNA) is a type of noncoding RNA with high stability, which has been shown to play an important role in biological processes and TME reprogramming in a variety of tumors. The biological function of a novel circRNA, circATP2B4, in epithelial ovarian cancer (EOC) was detected and evaluated. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of extracellular vesicles (EV)-packaged circATP2B4. Macrophage uptake of circATP2B4 was determined by EVs tracing. Dual luciferase reporter, FISH, Western blotting, and flow cytometry assays were used to investigate the interactions between circATP2B4 and miR-532-3p as well as sterol regulatory element-binding factor 1 (SREBF1) expression in macrophages. CircATP2B4 was upregulated in EOC tissues and positively correlated with ovarian cancer progression. Functionally, circATP2B4 promoted carcinogenic progression and metastasis of EOC both in vitro and in vivo. Mechanistically, EV-packaged circATP2B4 in EOC could be transmitted to infiltrated macrophages and acted as competing endogenous RNA of miR-532-3p to relieve the repressive effect of miR-532-3p on its target SREBF1. Furthermore, circATP2B4 induced macrophage M2 polarization by regulating the miR-532-3p/SREBF1/PI3Kα/AKT axis, thereby leading to immunosuppression and ovarian cancer metastasis. Collectively, these data indicate that circATP2B4-containing EVs generated by EOC cells promoted M2 macrophages polarization and malignant behaviors of EOC cells. Thus, targeting EVs-packaged circATP2B4 may provide a potential diagnosis and treatment strategy for ovarian cancer.

Low-dose BPA and its substitute BPS promote ovarian cancer cell stemness via a non-canonical PINK1/p53 mitophagic signaling.

The environmental toxicity of bisphenol A (BPA) and its analog like bisphenol S (BPS) have drawn wide attention, but their roles in cancer progression remain controversial. Here, we investigated the effect of BPA/BPS on the development of ovarian cancer. Human internal BPA/BPS exposure levels were analyzed from NHANES 2013-2016 data. We treated human ovarian cancer cells with 0-1000 nM BPA/BPS and found that 100 nM BPA/BPS treatment significantly increased Cancer Stem Cell (CSC) markers expression including OCT4, NANOG and SOX2. Cancer cell stemness evaluation induced by BPA/BPS was notably attenuated by the knockdown of PINK1 or Mdivi-1 treatment. The activation of PINK1 initiated mitophagy by inhibiting p-p53 nuclear translocation in a non-canonical manner. In vivo studies validated that BPA/BPS-exposed mice have higher tumor metastasis incidence compared with the control group, while mitophagy inhibition blocked such a promotion effect. In addition, CSC markers such as SOX2 had been found to be overexpressed in the tumor tissues of BPA/BPS exposure group. Taken together, the findings herein first provide the evidence that environmentally relevant BPA/BPS exposure could enhance ovarian cancer cell stemness through a non-canonical PINK1/p53 mitophagic pathway, raising concerns about the potential population hazards of BPA and other bisphenol analogs.

Global Burden and Trends in Incidence, Mortality, and Disability of Stomach Cancer From 1990 to 2017.

INTRODUCTION: Stomach cancer is a serious global public health problem. The current burden of stomach cancer and its trends across time and location need to be understood to develop effective preventive strategies. METHODS: Data were obtained from the Global Burden of Disease study. The burden of stomach cancer and variations in time and geographical regions were assessed according to the age-standardized rate and estimated annual percentage change (EAPC) of the incidence and mortality rate between 1991 and 2017. We also investigated the associations between the relevant rates and sociodemographic index (SDI). RESULTS: Overall, the age-standardized incidence rate (EAPC = -1.36, 95% confidence interval [CI]: -1.47 to -1.25), age-standardized mortality rate (EAPC = -2.2, 95% CI: -2.29 to -2.12), and age-standardized disability-adjusted life years rate (EAPC = -2.52, 95% CI: -2.63 to -2.43) decreased worldwide from 1990 to 2017. This trend varied across different countries and regions and according to sex and age. SDI had a significant negative correlation with the age-standardized mortality rate (P < 0.01, r = -0.28) and age-standardized disability-adjusted life years rate (P < 0.01, r = -0.31). Similar negative correlations were observed between SDI and the EAPC. DISCUSSION: The observed correlation between SDI and disease burden suggests that strategically implementing the screening and eradication of Helicobacter pylori, improving the medical level in countries with low SDI, and promoting the implementation of tobacco cessation policies would help reduce the disease burden of stomach cancer.

[Correlation between spirit-qi acupuncture and lifting-thrusting twirling method for spirit in Huangdi Neijing].

By analyzing the articles in Huangdi Neijing (Inner Canon of Yellow Emperor), combined with the verification of consciousness in vitro in clinic and modern science, it is found Huangdi Neijing has made special requirements of treating spirit for physicians using spirit-qi acupuncture. The physicians consciously use different methods to motivate the spirit of physician and patients, especially patients, to transform it to the physiological effect of patients, which could minimize the psychological factors that make negative influence on treatment; also the psychotherapy is considered as the most important principle of treating spirit. The reinforcing and reducing methods in later generations, mainly lifting-thrusting twirling method, unintentionally lead patients into a basic or strong status of treating spirit or keeping spirit during the process of achieving stimulation and needle sensation. To partially perform the special role of treating spirit for physicians in Huangdi Neijing on patients could cause the chages including patient-based using spirit to move qi. It not only inspires the body's natural resistance to disease and self-healing, but also motivates the self-protection mechanism of keeping spirit.

[Profound meaning of acupuncture taboos in Internal Classic based on the fault of reinforcing and reducing technique by mind conduction of acupuncture therapy].

By analyzing the acupuncture taboos in Neijing (Internal Classic) on clinical application of mind conduction of acupuncture therapy in going against the actual situation, astronomy and others, it is found that the relevant acupuncture taboo implies many subtle mysteries of human body, qi, mind and astronomy, which have not been discovered yet in modern science and are very significant in qi protection. In Neijing, the acupuncture physicians have been highly required in the mind treatment, in which, accurately regulating qi circulation is the target in the treatment. The mind conduction is used for qi circulation to accomplish accurately the reinforcing or reducing in the deficiency or excess condition. All of the taboos are provided to normalize the accuracy of reinforcing and reducing technique of acupuncture therapy and avoid the damage of qi in human body. Hence, those taboos must be obeyed so as to prevent from serious consequence and ensure the safety of this acupuncture therapy.

[Clinical research of lumbar strain of cold damp pattern treated with acupuncture with the consciousness conduction involved].

OBJECTIVE: To compare the efficacy between the reducing technique with consciousness conduction involved and the reducing technique by needle rotation of acupuncture in the treatment of lunbar strain of cold damp pattern. METHODS: One hundred and eight patients were randomized into group A and group B, 54 cases in each one. Ashi points were the main points in the two groups. In the group A, the reducing technique with consciousness conduction involved was applied to ashi points. In the group B, the reducing technique with needle rotation was adopted. Cupping and the irradiation specific electromagnetic wave apparatus (TDP) were used in the two groups as the adjuvant therapy. The treatment was given once every two days, and 10 treatments made one session. The treatment stopped till pain disappeared. The efficacy was evaluated in 1 session of treatment. The numerical rating scale (NRS) and the Oswestry disability index (ODI) were observed before and at the end of treatment. NRS of acupuncture itself was observed at the end of treatment. The recurrence rate was compared between the two groups. RESULTS: The curative and remarkably effective rate was 87.0% (47/54) in the group A, better than 63.0% (34/54) in the group B (P < 0.01). After treatment, NRS and ODI scores were all reduced as compared with those before treatment in the two groups (both P < 0.01). The results in the group A were better than those in the group B (both P < 0.01). Three months after treatment, the recurrence rate was 3.8% (2/52) in the group A, better than 17.7% (9/51, P < 0.05) in the group B. Pain induced by acupuncture itself was mild in the two groups and NRS score in the group A was lower than that in the group B (P < 0.01). CONCLUSION: Acupuncture with the consciousness conduction involved is superior to the reducing technique with needle rotation in the treatment of lumbar strain of cold damp pattern, in which, pain induced by acupuncture itself is much milder than that induced by the reducing technique with needle rotation.

[Efficacy observation on supraspinal ligament injury in deficiency syndrome treated with acupuncture at Dazhong (KI 4) only].

OBJECTIVE: To compare the efficacy difference on the treatment of supraspinal ligament injury in deficiency syndrome between only-puncturing at Dazhong (KI 4) and routine acupuncture therapy and then explore an optimum process. METHODS: One hundred and twenty-six cases were randomly divided into a Dazhong group (63 cases) and a routine acupuncture group (63 cases). Based on the same treatment including TDP irradiation, cupping at Shenshu (BL 23), Dachangshu (BL 25), Mingmen (GV 4), Yaoyangguan (GV 3) and Ashi points, the patients in the Dazhong group received only-puncturing Dazhong (KI 4) with respiratory reinforcing method once daily or every other day, three times of which made a course of the treatment, with on interval of one day or without between different courses. For the routine acupuncture group, the same reinforcing method was applied at shenshu (BL 23) pointect, and the other requirements such as courses were also the same. RESULTS: The cured and markedly effective rate was 88.9% (56/63) in the Dazhong group, which was significantly superior to that of 54.0% (34/63) in the routine acupuncture group (P < 0.01). Compared before and after the treatment, the score of Numerical Rating Scale (NRS) and the clinical symptom score of the two groups were significantly decreased (all PF < 0.01). Compared between the two groups, there were significant differences in NRS and clinical symptom score the Dazhong group was better than the routine acupuncture group (both P < 0.01). CONCLUSION: The only-puncturing Dazhong (KI 4) method combined with cupping and TDP irradiation are simple and effective for supraspinal ligament injury in deficiency syndrome.