The fish reproductive system is a complex biological system. Nonetheless, reproductive organ development is conserved, which starts with sex determination and then sex differentiation. The sex of a teleost is determined and differentiated from bipotential primordium by genetics, environmental factors, or both. These two processes are species-specific. There are several prominent genes and environmental factors involved during sex determination and differentiation. At the cellular level, most of the sex-determining genes suppress the female pathway. For environmental factors, there are temperature, density, hypoxia, pH, and social interaction. Once the sexual fate is determined, sex differentiation takes over the gonadal developmental process. Environmental factors involve activation and suppression of various male and female pathways depending on the sexual fate. Alongside these factors, the role of the brain during sex determination and differentiation remains elusive. Nonetheless, GnRH III knockout has promoted a male sex-biased population, which shows brain involvement during sex determination. During sex differentiation, LH and FSH might not affect the gonadal differentiation, but are required for regulating sex differentiation. This review discusses the role of prominent genes, environmental factors, and the brain in sex determination and differentiation across a few teleost species.

Vitamin E acts as an antioxidant and reduces the level of reactive oxygen species (ROS) in Alzheimer’s disease (AD). Alpha-tocopherol (ATF) is the most widely studied form of vitamin E besides gamma-tocopherol (GTF) which also shows beneficial effects in AD. The levels of amyloid-beta (Aβ) and amyloid precursor protein (APP) increased in the brains of AD patients, and mutations in the APP gene are known to enhance the production of Aβ. Mitochondrial function was shown to be affected by the increased level of Aβ and may induce cell death. Here, we aimed to compare the effects of ATF and GTF on their ability to reduce Aβ level, modulate mitochondrial function and reduce the apoptosis marker in SH-SY5Y cells stably transfected with the wild-type or mutant form of the APP gene. The Aβ level was measured by ELISA, the mitochondrial ROS and ATP level were quantified by fluorescence and luciferase assay respectively whereas the complex V enzyme activity was measured by spectrophotometry. The expressions of genes involved in the regulation of mitochondrial membrane permeability such as voltage dependent anion channel (VDAC1), adenine nucleotide translocase (ANT), and cyclophilin D (CYPD) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), while the expressions of cyclophilin D (CypD), cytochrome c, Bcl2 associated X (BAX), B cell lymphoma-2 (Bcl-2), and pro-caspase-3 were determined by western blot. Our results showed that mitochondrial ROS level was elevated accompanied by decreased ATP level and complex V enzyme activity in SH-SY5Y cells expressing the mutant APP gene (p < 0.05). Treatment with both ATF and GTF reduced the mitochondrial ROS level with maximum reduction was observed in the cells treated with high concentrations of ATF and GTF (p < 0.05). However, only GTF at 80 µM significantly increase the ATP level and complex V enzyme activity (p < 0.05). VDAC1 and CYPD were downregulated and CypD protein was significantly overexpressed in cells transfected with the wild-type (WT) and mutant APP gene (p < 0.05). Cytochrome c release, the ratio of BAX/Bcl-2, and pro-caspase-3 expression increased in cells expressing mutated APP gene (p < 0.05). The expression of CypD and pro-caspase 3 protein, and the ratio of BAX/Bcl-2 were increased in the following order; SH-SY5Y-APP-WT < SH-SY5Y-APP Swe <SH-SY5Y-APP Swe/Ind. Treatment with both ATF and GTF reduced the release of cytochrome c and the ratio of BAX/Bcl-2. However, only GTF significantly reduced the expression of CypD and pro-caspase-3, suggestive of its unique role in AD. In conclusion, GTF has an effect that was not shown by ATF and thus suggest its potential role in the development of therapeutic agents for AD.

The king of rivers or mahseer comprises three genera: Tor, Neolissochilus, and Naziritor, under the Cyprinidae family. The Tor genus has been classified as the true mahseer due to the presence of a median lobe among the three genera. The Tor species are widely distributed across Southeast (SE) Asia, and 13 Tor species have been reported previously: Tor ater, Tor dongnaiensis, Tor douronensis, Tor laterivittatus, Tor mosal, Tor mekongensis, Tor putitora, Tor sinensis, Tor soro, Tor tambra, Tor tambroides, Tor tor and Tor yingjiangensis. However, the exact number of valid Tor species remains debatable. Different and unstandardized approaches of applying genetic markers in taxonomic identification and morphology variation within the same species have further widened the gap and ameliorated the instability of Tor species taxonomy. Therefore, synchronized and strategized research among Tor species researchers is urgently required to improve and fill the knowledge gap. This review is a current update of SE Asia’s Tor species, outlining their distribution, morphology, and genetic identification. In addition, the present review proposes that there are ten valid Tor species in the SE Asian region. This list will serve as a template and standard to improve the taxonomy of the SE Asian Tor species, which could serve as a basis to open new directions in Tor research.

Tocotrienol-rich fraction (TRF) is palm vitamin E that consists of tocopherol and tocotrienol. TRF is involved in important cellular regulation including delaying cellular senescence. A key regulator of cellular senescence, Sirtuin 1 (SIRT1) is involved in lipid metabolism. Thus, SIRT1 may regulate vitamin E transportation and bioavailability at cellular level. This study aimed to determine the role of SIRT1 on cellular uptake and bioavailability of TRF in human diploid fibroblasts (HDFs). SIRT1 gene in young HDFs was silenced by small interference RNA (siRNA) while SIRT1 activity was inhibited by sirtinol. TRF treatment was given for 24 h before or after SIRT1 inhibition. Cellular concentration of TRF isomers was determined according to the time points of before and after TRF treatment at 0, 24, 48, 72 and 96 h. Our results showed that all tocotrienol isomers were significantly taken up by HDFs after 24 h of TRF treatment and decreased 24 h after TRF treatment was terminated but remained in the cell up to 72 h. The uptake of α-tocopherol, α-tocotrienol and β-tocotrienol was significantly higher in senescent cells as compared to young HDFs indicating higher requirement for vitamin E in senescent cells. Inhibition of SIRT1 gene increased the uptake of all tocotrienol isomers but not α-tocopherol. However, SIRT1 inhibition at protein level decreased tocotrienol concentration. In conclusion, SIRT1 may regulate the cellular uptake and bioavailability of tocotrienol isomers in human diploid fibroblast cells while a similar regulation was not shown for α-tocopherol.

Phoenixin (PNX) is an emerging neuropeptide that plays a significant role in regulating metabolism and reproduction. This comprehensive review examines findings from human, in vivo, and in vitro studies to elucidate the functions of PNX in metabolic processes. PNX has been identified as a key player in essential metabolic pathways, including energy homeostasis, glucose, lipid and electrolyte metabolism, and mitochondrial dynamics. It modulates food and fluid intake, influences glucose and lipid profiles, and affects mitochondrial biogenesis and function. PNX is abundantly expressed in the hypothalamus, where it plays a crucial role in regulating reproductive hormone secretion and maintaining energy balance. Furthermore, PNX is also expressed in peripheral tissues such as the heart, spleen, and pancreas, indicating its involvement in the regulation of metabolism across central and peripheral systems. PNX is a therapeutic peptide that operates through the G protein-coupled receptor 173 (GPR173) at the molecular level. It activates signaling pathways such as cAMP-protein kinase A (PKA) and Epac-ERK, which are crucial for metabolic regulation. Research suggests that PNX may be effective in managing metabolic disorders like obesity and type 2 diabetes, as well as reproductive health issues like infertility. Since metabolic processes are closely linked to reproduction, further understanding of PNX’s role in these areas is necessary to develop effective management/treatments. This review aims to highlight PNX’s involvement in metabolism and identify gaps in current knowledge regarding its impact on human health. Understanding the mechanisms of PNX’s action is crucial for the development of novel therapeutic strategies for the treatment of metabolic disorders and reproductive health issues, which are significant public health concerns globally.

Ovarian cancer (OC) remains the deadliest gynecological malignancy, with alarming projections indicating a 42% increase in new cases and a 51% rise in mortality by 2040. This review explores the challenges in OC treatment, focusing on chemoresistance mechanisms and the potential of extracellular vesicles (EVs) as drug delivery agents. Despite advancements in treatment strategies, including cytoreductive surgery, platinum-based chemotherapy, and targeted therapies, the high recurrence rate underscores the need for innovative approaches. Key resistance mechanisms include drug efflux, apoptosis disruption, enhanced DNA repair, cancer stem cells, immune evasion, and the complex tumor microenvironment. Cancer-associated fibroblasts and extracellular vesicles play crucial roles in modulating the tumor microenvironment and facilitating chemoresistance. EVs, naturally occurring nanovesicles, emerge as promising drug carriers due to their low toxicity, high biocompatibility, and inherent targeting capabilities. They have shown potential in delivering chemotherapeutics like doxorubicin, cisplatin, and paclitaxel, as well as natural compounds such as curcumin and berry anthocyanidins, enhancing therapeutic efficacy while reducing systemic toxicity in OC models. However, challenges such as low production yields, heterogeneity, rapid clearance, and inefficient drug loading methods need to be addressed for clinical application. Ongoing research aims to optimize EV production, loading efficiency, and targeting, paving the way for novel and more effective therapeutic strategies in OC treatment. Overcoming these obstacles is crucial to unlocking the full potential of EV-based therapies and improving outcomes for OC patients.