ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.

Objective　To investigate the biological characteristics of the serine protease inhibitor 15 (RmS-15) protein of Rhipicephalus microplus, and to perform molecular cloning and prokaryotic expression. Methods RmS-15 gene was amplified and sequenced to construct a phylogenetic tree to understand its evolutionary relationships. Bioinformatic tools were used to analyze the physicochemical properties, signal peptide, secondary and tertiary structure of the RmS-15 protein. In addition, DNA star and ABCpred were used to predict potential B-lymphocyte antigenic epitopes of RmS-15 protein, and potential T-lymphocyte antigenic epitopes were predicted by SYF-PEITHI and IEDB. Finally, the RmS-15 recombinant protein of Rhipicephalus microplus was obtained using the E.coli prokaryotic expression system and purified. Results The RmS-15 gene with 1 212 bp was successfully amplified, encoding a protein comprising 403 amino acids. Phylogenetic tree results indicated high conservation of the RmS-15 protein among different tick amino acid sequences, with the closest phylogenetic relationships to the Rhipicephalus haemaphysaloides and the Rhipicephalus sanguineus. The results of physicochemical property analysis showed a 20-amino acid signal peptide at the N-terminus of the RmS-15 protein, with a relative molecular weight and theoretical isoelectric point of 44 000 and 6.68, respectively. The protein showed an average hydrophilicity of 0.001, classifying it as a stably hydrophilic protein. The results of antigenicity analysis showed that the dominant fragments of B-cell antigenic epitopes of RmS-15 protein were 102-112 aa,147-152 aa and 207-215 aa, and the dominant fragments of T-cell antigenic epitopes were 3-11 aa, 6-14 aa, 27-33 aa, 34-37 aa. Protein expression results showed that RmS-15 protein exhibited high expression levels in the supernatant after induction with 0.8 mmol/L IPTG at 16 ℃ for 24 hours and reached a successful purification with a single band of the protein molecular weight of 44 000. Conclusions The method of prokaryotic expression and purification of RmS-15 protein from Rhipicephalus microplus was successfully established. Bioinformatics analysis demonstrated its strong antigenicity, suggesting its potential to develop as a candidate vaccine for ticks.

Objective To investigate the protective effect of berberine (BBR) against ionizing radiation injury in rats and its mechanism of action. Methods Sprague-Dawley rats were divided into seven groups: normal control group, 1-Gy radiation group, 1-Gy radiation plus low-dose BBR (50 mg/kg) group, 1-Gy radiation plus high-dose BBR (150 mg/kg) group, 3-Gy radiation group, 3-Gy radiation plus low-dose BBR (50 mg/kg) group, and 3-Gy radiation plus high-dose BBR (150 mg/kg) group. All the groups except the normal control group were exposed to external irradiation with a medical electron linear accelerator, followed by BBR administration by gavage for consecutive ten days. The serum levels of superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) were measured by using the micromethod. The pathological changes of the bone marrow and small intestine were observed with HE staining. Results Compared with the normal control group, the radiation groups showed significantly increased MDA levels (P < 0.05), significantly decreased SOD and GSH levels (P < 0.05), and more severe pathological damage of the bone marrow and small intestine. Compared with the radiation groups, the BBR groups showed significantly decreased MDA levels (P < 0.05), significantly increased SOD and GSH levels (P < 0.05), and reduced pathological damage to the bone marrow and small intestine, which were more marked in the high-dose BBR group. Conclusion BBR has a certain protective effect against radiation injury in rats, which may be through increasing the activity of antioxidant substances, enhancing free radical clearance, and thereby alleviating free radicals-caused oxidative damage.

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

【Objective】 To establish the reference interval of Thromboelastography(TEG)of healthy adult in Hainan, compare with the interval provided by the manufacturers, and analyze the influencing factors. 【Methods】 A total of 308 healthy adult volunteers were included according to the inclusion and exclusion criteria. The TEG was analyzed based on adequate quality control, and the reference interval of each parameter was calculated with 95% CI. 【Results】 The reference interval of these volunteers were R 4.27~9.20 min, K 1.60~3.83 min, Angle 44.22°~67.78°, MA 47.82~64.17 mm, CI -5.63~1.12 and G 4.58~9.03. 14.94% (46/308) of these volunteers had at least one index exceeded the reference interval provided by manufacturers. A total of 74 healthy volunteers were diagnosed with coagulation disorder, with the specificity at 79.22%. Significant differences of R, K, Angle, MA, CI, G were observed between males and females (P<0.05). Hypercoagulability was not associated with the age. 【Conclusion】 This study established a reference interval of TEG of healthy adults in Hainan, which provided reference for related clinical and basic science study.

【Objective】 To investigate the correlation between preoperative thromboelastography (TEG) parameters and routine coagulation tests of malignant tumor patients. 【Methods】 A total of 79 patients with malignant tumors, receiving preoperative TEG tests and routine coagulation tests between January 2019 and June 2020, were included. The correlation and regression between coagulation indexes and TEG parameters were analyzed. 【Results】 In patients with malignant tumors, the coagulation time(K) was negatively correlated with Plt and fibrinogen (FIB), while Angle, Ma, and G were respectively positively correlated with Plt and FIB. 【Conclusion】 There is a correlation between preoperative TEG parameters and routine coagulation tests in patients with malignant tumors. There is complementarity but not reciprocal substitutability between these two tests.

Objective:To explore the feasibility of autologous transplantation of frozen-thawed ovarian tissue to induce pubertal development in adolescent females.Methods:Before hematopoietic stem cell transplantation in patient with severe β-thalassemia, 11 pieces of ovarian tissue were frozen in the Center of Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University in 2019. The patient was diagnosed as premature ovarian failure after hematopoietic stem cell transplantation. There were no signs of puberty development and menarche. Orthotopic ovarian tissue transplantation was performed for the patient through laparoscopy, and a total of 5 pieces of ovarian tissue were transplanted on January 20, 2022. Postoperatively, we followed up the sex hormone levels, growth and development of the patients and menarche.Results:The patient developed menarche 5 months after ovarian transplantation. The levels of sex hormones showed that follicle-stimulating hormone and luteinizing hormone were significantly decreased, and estradiol levels were significantly increased, indicating that ovarian tissue transplantation was successful, and follicles had begun to recruit and develop. The patient's ultrasonography revealed a markedly enlarged uterus and a thickened endometrium. Antral follicles were detected in the left implantation site of pelvic cavity.Conclusion:Cryopreservation of ovarian tissue is recommended for fertility preservation in prepubertal children. Autologous frozen-thawed ovarian tissue transplantation can induce natural puberty development and restore the reproductive endocrine function in children with ovarian failure, delayed puberty development or even stagnation.

Objective:To explore the feasibility of autologous transplantation of frozen-thawed ovarian tissue to induce pubertal development in adolescent females.Methods:Before hematopoietic stem cell transplantation in patient with severe β-thalassemia, 11 pieces of ovarian tissue were frozen in the Center of Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University in 2019. The patient was diagnosed as premature ovarian failure after hematopoietic stem cell transplantation. There were no signs of puberty development and menarche. Orthotopic ovarian tissue transplantation was performed for the patient through laparoscopy, and a total of 5 pieces of ovarian tissue were transplanted on January 20, 2022. Postoperatively, we followed up the sex hormone levels, growth and development of the patients and menarche.Results:The patient developed menarche 5 months after ovarian transplantation. The levels of sex hormones showed that follicle-stimulating hormone and luteinizing hormone were significantly decreased, and estradiol levels were significantly increased, indicating that ovarian tissue transplantation was successful, and follicles had begun to recruit and develop. The patient's ultrasonography revealed a markedly enlarged uterus and a thickened endometrium. Antral follicles were detected in the left implantation site of pelvic cavity.Conclusion:Cryopreservation of ovarian tissue is recommended for fertility preservation in prepubertal children. Autologous frozen-thawed ovarian tissue transplantation can induce natural puberty development and restore the reproductive endocrine function in children with ovarian failure, delayed puberty development or even stagnation.

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.