Endosulfan affects embryonic development synergistically under elevated ambient temperature.

In the present study, we determined the developmental toxicity of endosulfan at an elevated ambient temperature using the zebrafish animal model. Zebrafish embryos of various developmental stages were exposed to endosulfan through E3 medium, raised under two selected temperature conditions (28.5 °C and an elevated temperature of 35 °C), and monitored under the microscope. Zebrafish embryos of very early developmental stages (cellular cleavage stages, such as the 64-cell stage) were highly sensitive to the elevated temperature as 37.5% died and 47.5% developed into amorphous type, while only 15.0% of embryos developed as normal embryos without malformation. Zebrafish embryos that were exposed concurrently to endosulfan and an elevated temperature showed stronger developmental defects (arrested epiboly progress, shortened body length, curved trunk) compared to the embryos exposed to either endosulfan or an elevated temperature. The brain structure of the embryos that concurrently were exposed to the elevated temperature and endosulfan was either incompletely developed or malformed. Furthermore, the stress-implicated genes hsp70, p16, and smp30 regulations were synergistically affected by endosulfan treatment under the elevated thermal condition. Overall, the elevated ambient temperature synergistically enhanced the developmental toxicity of endosulfan in zebrafish embryos.

Phytochemical Analysis and Understanding the Antioxidant and Anticancer Properties of Methanol Extract from Litsea glutinosa: In Vitro and In Vivo Studies.

Litsea glutinosa (L. glutinosa) is considered an evidence-based medicinal plant for the treatment of cancer, the leading cause of death worldwide. In our study, the in vitro antioxidant and in vivo anticancer properties of an essential ethno-medicinal plant, L. glutinosa, were examined using non-toxic doses and a phytochemical analysis was executed using gas-chromatography-mass-spectrometry. The in vitro antioxidant study of the L. glutinosa methanolic extract (LGBME) revealed a concentration-dependent antioxidant property. The bark extract showed promising antioxidant effects in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. The strongest antioxidant activity was demonstrated at the maximum concentration (50 µg/mL). The IC50 values of the LGBME and BHT were 5.51 and 5.01 µg/mL, respectively. At the same concentration, the total antioxidant capacity of the LGBME was 0.161 µg/mL and the ferric reducing antioxidant power assay result of the LGBME was 1.783 µg/mL. In the cytotoxicity study, the LD50 of the LGBME and gallic acid were 24.93 µg/mL and 7.23 µg/mL, respectively. In the in vivo anticancer-activity studies, the LGBME, particularly at a dose of 150 mg/kg/bw, showed significant cell-growth inhibition, decreased tumor weight, increased mean survival rate, and upregulated the reduced hematological parameters in EAC (Ehrlich's ascites carcinoma)-induced Swiss albino mice. The highest cell-growth inhibition, 85.76%, was observed with the dose of 150 mg/kg/bw. Furthermore, the upregulation of pro-apoptotic genes (p53, Bax) and the downregulation of anti-apoptotic Bcl-2 were observed. In conclusion, LGBME extract has several bioactive phytoconstituents, which confirms the antioxidant and anticancer properties of L. glutinosa.

The genus Alphitonia Reissek ex Endl. (Rhamnaceae): A review of its customary uses, phytochemistry and biological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Alphitonia Reissek ex Endl. is a relatively small genus of the family Rhamnaceae. Plants of this genus are found predominantly in the tropical regions of Southeast Asia, Australia and the Pacific, with some species being widely distributed and others endemic to a region. Almost half of the species of the Alphitonia genus have been reported for their customary (traditional and contemporary) medicinal uses. This includes for the treatment of skin conditions, headache, stomachache, inflammation, and body pain such as joint pain and childbirth. AIM OF THE REVIEW: The aim of this review is to provide the first comprehensive account on the customary uses including ethnomedicinal uses, and phytochemistry and biological activities of the Alphitonia genus, and to identify gaps in current knowledge and scope for future research of plants of this genus. MATERIALS AND METHODS: Information relevant to the genus Alphitonia was collected by searching the scientific databases (SciFinder, Google Scholar, ACS publications, PubMed, Wiley Online Library and International Plant name Index). Species names were validated using the World Flora Online database (www.worldfloraonline.org). RESULTS: Eight plants from the Alphitonia genus have been reported to be used as customary medicines, i.e. A. excelsa, A. ferruginea, A. franguloides, A. incana, A. neocaledonica, A. petriei, A. philippinensis and A. zizyphoides. A. excelsa, A. petriei, A. philippinensis and A. zizyphoides, have been shown to have biological activities that align with their customary uses, including antimicrobial, antioxidant and anti-inflammatory activities. Only five Alphitonia species reported for their medicinal customary uses have been explored for their phytochemistry, i.e. A. excelsa, A. neocaledonica, A. petriei, A. philippinensis and A. zizyphoides. Compounds identified from these plants include those that are well known for their medicinal importance. A. macrocarpa, A. whitei and A. xerocarpus have also been examined for their phytochemistry and have been found to have the same or similar bioactive compounds to those found in customarily used Alphitonia species. No biological activities or phytochemistry studies have been reported for the known customarily used medicinal plants A. ferruginea, A. franguloides and A. incana. CONCLUSIONS: This review highlights the customary uses, biological activities and phytochemistry of plants of the Alphitonia Reissek ex Endl. genus and highlights the significance of the knowledge systems of Indigenous peoples. Of the plants that have been researched for their biological activities and phytochemistry, there is good correlation with these properties and their customary medicinal uses. However, over half of the plants of the Alphitonia genus, including those that are already reported in the public domain for their customary medicinal uses, have had none or limited biological activities or phytochemistry studies conducted. While only eight species of the Alphitonia genus have been reported as customary medicines, other Alphitonia species also possess medicinally important compounds, and it is possible that they are customary medicines but their uses have not been shared publicly by the Indigenous knowledge custodians. There is clearly much scope for further investigation of this genus with regards to their ethnomedicinal uses and therapeutic potential.

Carbofuran affects cellular autophagy and developmental senescence through the impairment of Nrf2 signalling.

Carbofuran is a broad-spectrum synthetic pesticide. Its exposure to non-target mammals affects the biological system through the induction of oxidative stress. Since oxidative stress is a major contributing factor to cellular autophagy and senescence, our present investigation determined the impacts of carbofuran-induced oxidative stress on cellular autophagy and senescence. A transmembrane protein, Spinster homolog 1 (Spns1), is involved in autophagic lysosomal metabolism. Its mutation accelerates the cellular senescence and shortens the lifespan. Using a transgenic zebrafish line, expressing fluorescent microtubules-associated protein 1 light chain 3 (EGFP-LC3) at the membrane of the autophagosome, we found that carbofuran affects autophagic lysosomal biogenesis in wild-type zebrafish and exacerbates autophagic defect in spns1-mutant zebrafish. In real-time mortality study, carbofuran has shortened the lifespan of wild-type fish. Nrf2 is a stress-responsive transcription factor that regulates the expression of antioxidant genes (such as gstp1) in the prevention of oxidative stress-mediated cellular damage. To assess the effect of carbofuran on Nrf2 signalling, we established a dual-monitoring transgenic zebrafish line, expressing gstp1 promoter-driven EGFP and mCherry-tagged Neh2 domain of Nrf2. Our results suggested that the exposure of carbofuran has down-regulated both Nrf2 and Gstp1 expressions. Overall, carbofuran affects cellular autophagy and accelerates senescence by enervating the Nrf2 signalling.

Barriers in access to healthcare services for individuals with disorders of sex differentiation in Bangladesh: an analysis of regional representative cross-sectional data.

BACKGROUND: Worldwide people in disorder of sex development (DSD) faces multiple barriers while seeking their social rights, particularly healthcare services. We aimed to explore the healthcare opportunities available to them, using patterns of healthcare utilization and difficulties faced by DSD population in accessing healthcare services in Bangladesh. METHODS: Data from a total of 945 DSD population and 71 medical staff were analyzed, collected from three major divisions (Dhaka, Chittagong, and Rajshahi) in Bangladesh during the period of January to December of 2017. A structured questionnaire was used to collect data via face-to-face interviews. Descriptive statistic was used to determine the frequencies of the visit by the DSD population in healthcare facilities as well as to analyze difficulties experienced by the DSD population in getting healthcare services. Multivariate regression analysis was used to explore the association between perceived barriers in getting healthcare services and failures of the DSD population to receive the healthcare services. RESULTS: Present data revealed that around 80% of DSD population sought healthcare services from government healthcare facilities, where the overall success rate in getting healthcare services was less than 50%. The DSD population reported a number of reasons for failures in getting healthcare services, including non-friendly interaction by non-clinical hospital's staff, non-friendly interaction by physicians, public fright as general people do not want to mingle with a DSD person, undesirable excess public interest in DSD individuals, and limitation of the treatment opportunities of hospitals to merely male or female patients. Among the stated reasons, the most frequently reported reason was non-friendly interaction by physicians (50.27%), followed by undesirable excess public interest in DSD individuals (50.16%). CONCLUSION: DSD population in Bangladesh have limited access to healthcare facilities and facing multiple barriers to get healthcare services. Initiatives from the government and social organizations are important to ensure their access to healthcare services.

Bioactivity and chemical characterisation of Lophostemon suaveolens--an endemic Australian Aboriginal traditional medicinal plant.

Lophostemon suaveolens is a relatively unexplored endemic medicinal plant of Australia. Extracts of fresh leaves of L. suaveolens obtained from sequential extraction with n-hexane and dichloromethane exhibited antibacterial activity in the disc diffusion and MTT microdilution assays against Streptococcus pyogenes and methicillin sensitive and resistant strains of Staphylococcus aureus (minimum bactericidal concentration < 63 µg/mL). The dichloromethane extract and chromatographic fractions therein inhibited nitric oxide in RAW264.7 murine macrophages (IC50 3.7-11.6 µg/mL) and also PGE2 in 3T3 murine fibroblasts (IC50 2.8-19.7 µg/mL). The crude n-hexane, dichloromethane and water extracts of the leaves and chromatographic fractions from the dichloromethane extract also showed modest antioxidant activity in the ORAC assay. GC-MS analysis of the n-hexane fraction showed the presence of the antibacterial compounds aromadendrene, spathulenol, ß-caryophyllene, α-humulene and α-pinene and the anti-inflammatory compounds ß-caryophyllene and spathulenol. Fractionation of the dichloromethane extract led to the isolation of eucalyptin and the known anti-inflammatory compound betulinic acid.

Antimicrobial activity of customary medicinal plants of the Yaegl Aboriginal community of northern New South Wales, Australia: a preliminary study.

BACKGROUND: This study is a collaboration between Macquarie University researchers and the Yaegl Aboriginal Community of northern NSW, Australia to investigate the antimicrobial potential of plants used in the topical treatment of wounds, sores and skin infections. Based on previously documented medicinal applications, aqueous and aqueous ethanolic extracts of Alocasia brisbanensis, Canavalia rosea, Corymbia intermedia, Hibbertia scandens, Ipomoea brasiliensis, Lophostemon suaveolens and Syncarpia glomulifera and the aqueous extracts of Smilax australis and Smilax glyciphylla were tested against common wound pathogens, including antibiotic resistant bacterial strains. METHODS: Plant material was prepared as aqueous extractions modelled on customary preparations and using 80% aqueous ethanol. Extracts were assayed against a selection of clinically relevant Gram positive (Streptococcus pyogenes and sensitive and resistant strains of Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa, Escherichia coli and Salmonella typhimurium) bacteria and a fungus (Candida albicans) using disc diffusion and MTT microdilution methods. Viability of treated microorganisms was determined by subculturing from microdilution assays. RESULTS: The extracts of Corymbia intermedia, Lophostemon suaveolens and Syncarpia glomulifera had promising levels of antimicrobial activity (MIC 31-1,000 µg/mL) against both antibiotic sensitive and resistant Staphylococcus aureus as well as the fungus Candida albicans (clinical isolate). CONCLUSION: Aqueous and 80% aqueous ethanolic extracts of Lophostemon suaveolens, Corymbia intermedia and Syncarpia glomulifera exhibited promising levels of antimicrobial activity against a range of both antibiotic sensitive and resistant strains of microorganisms. This is the first report of antimicrobial activities for C. intermedia and L. suaveolens and the leaves of S. glomulifera. This study demonstrates the value of customary knowledge in the identification of new sources of antimicrobial treatments.

Antimicrobial, antileishmanial and cytotoxic compounds from Piper chaba.

The petroleum ether and chloroform extracts of the root of Piper chaba showed antimicrobial, antileishmanial and cytotoxic activities. Further bioactivity-guided fractionation led to the isolation of Bornyl piperate (1), piperlonguminine (2) and piperine (3). This is the first report of isolation of compounds (1) and (2) from P. chaba. It was observed that the isolated compounds (1 and 2) showed potent antifungal activity when compared with standard drug Nystatin, and significant cytotoxic activity with the IC50 values of 0.76 and 0.83 µg mL⁻¹, respectively. These compounds were also found to have weak antibacterial and antileishmanial activities. This is the first report about the antileishmanial activity of Piper isolates.