Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis

The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.     

An Improved Synthesis of 7, 8-Epoxy-1,3,11-cembratriene- 15R(α), 16-diol,a Cembranoid of Marine Origin with a Potent Cancer Chemopreventive Activity

An effective method for the synthesis of 7,8-epoxy-1,3,11-cembratriene- 15R(α),16-diol and its in vitro Epstein-Barr Virus Early Antigen (EBV-EA) Activation Chemopreventive Assay are reported. This semisynthetic product is a new cembranoid with a potent tumor inhibitory activity that is expected to be a lead compound for a new class of chemopreventive agents of marine origin.     

Resveratrol Reverses Cadmium Chloride-induced Testicular Damage and Subfertility by Downregulating p53 and Bax and Upregulating Gonadotropins and Bcl-2 gene Expression

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl₂-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl₂+NS, E) CdCl₂+vehicle, F) RES followed by CdCl₂ and M) CdCl₂ followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.     

Re-emergence of multi-drug resistant <Emphasis Type="Italic">Salmonella enterica</Emphasis> serovar Stanley from cattle

During 2009, Salmonella enterica subspecies enterica serovar Stanley isolates were recovered from cattle diagnostic specimens in southern Japan, and the isolates were examined to characterize the genetic determinants involved in this new pathogenicity that associated with mortality in cattle. All the isolates were multi-drug resistance exhibited resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, oxytetracycline, and kanamycin (ACSSuT-Km) encoded by bla _TEM, catA, aadA1, sul1, tet(A), and aphA1 genes, respectively. Class 1 integrons of 1.5-kb size were detected in all MDR isolates. The isolates harboured easily transferable plasmids of ca. 210-kb with the potential of transmitting resistance phenotype and genotype detected in the donor isolates. XbaI-digested PFGE patterns generated two related clusters implicated in the dissemination of multi-drug resistance amongst Salmonella Stanley isolates. An emergence of multi-drug resistant Salmonella Stanley amongst food-producing animals, including cattle is a threat to human health, as resistant isolates may be transmitted to humans through the food chain.     

Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.     

Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice

Sarcophine-diol (SD), one of the structural modifications of sarcophine, has shown chemopreventive effects on 12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor development in female CD-1 mice. The objective of this study was to determine the chemopreventive effects of SD on UVB-induced skin tumor development in hairless SKH-1 mice, a model more relevant to human skin cancer, and to determine the possible mechanisms of action. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into two groups having 27 mice in each group: control and SD treatment. The control group was topically treated with 100 μL acetone and SD treatment group was topically treated with SD (30 μg/100 μL in acetone) 1 hour before each UVB radiation for 32 weeks. Tumor counts were recorded on a weekly basis for 30 weeks. Effects of SD on the expression of caspases were investigated to elucidate the possible mechanism of action. The proteins from epidermal homogenates of experimental mice were used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8 and caspase-9 respectively. TUNEL assay was used for determining DNA fragmented apoptotic cells in situ. Results showed that at the end of experiment, tumor multiplicity in control and SD treatment groups was 25.8 and 16.5 tumors per mouse respectively. Furthermore, Topical treatment of SD induced DNA fragmented apoptotic cells by upgrading the expressions of cleaved caspase-3 and caspase-8. This study clearly suggested that SD could be an effective chemopreventive agent for UVB-induced skin cancer by inducing caspase dependent apoptosis.