Baobab Index

A pivotal factor in the immune evasion of hepatocellular carcinoma (HCC) is the excessive exhaustion of CD8

A precision medicine strategy is likely to be more impactful, when pharmacogenomics (PGx) guided selection of drugs and dosage wherever applicable is implemented across the globe. In regions where resources are disproportionately distributed, PGx implementation in routine clinical care can play a critical role in ensuring the optimal use of limited healthcare infrastructure. At present, PGx data from the majority of the distinct ethnic populations across Asia, Africa, and South America is limited. While international consortia, working groups, and scientific bodies have made significant contributions toward evaluating the evidence for PGx implementation, the majority of existing guidelines and recommendations are derived primarily from studies conducted in a limited number of ethnic groups. Precision Medicine Initiatives in countries like Korea, Taiwan, and Malaysia and PGx organizations like the African Institute of Biomedical Science and Technology (AiBST), Consortium for Genomics & Therapeutics in Africa (CGTA), implementation of pharmacogenetic testing for the effective care and treatment in Africa, Greater Middle East (GME) whole exome sequencing program, Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF), Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM), Latin American Network for Validation and Implementation of Pharmacogenomic Clinical Guidelines (RELIVAF), IndiGen initiative, Southeast Asian Pharmacogenomics Research Network (SEAPharm), are working toward consolidating the PGx presence in these regions.

Ovarian cancer is a highly heterogeneous malignancy with complex molecular underpinnings that extend beyond genomic mutations to encompass transcriptomic and epigenomic alterations. Advances in next-generation sequencing and bioinformatics have enabled comprehensive profiling of gene expression patterns, non-coding RNAs, DNA methylation, histone modifications, and chromatin accessibility, offering novel insights into ovarian tumor biology. Transcriptomic analyses reveal dysregulated coding and non-coding RNA networks, while epigenomic studies uncover epigenetic modifications that regulate gene expression and chromatin structure, together shaping the cancer phenotype. The integration of transcriptomic and epigenomic data through sophisticated bioinformatics pipelines allows the identification of key regulatory networks and molecular subtypes, enhancing our understanding of ovarian cancer heterogeneity and progression. Bioinformatics tools facilitate differential expression analysis, epigenetic mapping, and multi-omics data integration, revealing potential biomarkers and therapeutic targets. These approaches have also illuminated mechanisms of chemoresistance and immune evasion, providing avenues for personalized therapy and improved patient stratification. Datasets will be critical to harness the full potential of transcriptomic and epigenomic research. Ultimately, bioinformatics-driven insights into the ovarian cancer transcriptome and epigenome promise to inform early diagnosis, prognostication, and the development of targeted therapies, advancing precision oncology in this lethal.

Pharmacogenomic-related adverse drug reactions and treatment failure contribute to global morbidity. Evidence for PGx-guided therapy in sub-Saharan Africa remains limited with few implementation studies. This study evaluated the potential clinical utility and projected population-level impact of pharmacogenomic testing in Zimbabwe. A cross-sectional analysis used the Zimbabwe Essential Medicines List, DPWG guidelines, Zimbabwean genotype/phenotype data, and locally approved Summary of Product Characteristics. For the actionable gene-drug pairs identified, the number needed to genotype values were calculated from DPWG-defined absolute risk reduction and local genotype-phenotype frequencies. Potential clinical utility was assessed using the Clinical Implication Score framework and compared with Dutch population data. Among 308 medicines screened, 30 (9.7%) contained actionable pharmacogenomic biomarkers, corresponding to 38 gene-drug pairs, all classified as vital or essential medicines. Lower NNG values were observed for UGT1A1-atazanavir (5), UGT1A1-irinotecan (9), CYP2B6-efavirenz (26), and CYP2C9-phenytoin (25), whereas 61% of gene-drug pairs had NNG values > 1,000 compared with 47% in the Dutch population. Overall, 81.6% of PGx recommendations were concordant across populations, while 21.1% were reclassified, primarily due to differences in local genetic profiles and the limited inclusion of PGx information in the Zimbabwean SmPCs, with 42% lacking PGx information compared with 24% in the Dutch dataset. Many essential medicines in Zimbabwe have actionable pharmacogenomic biomarkers, but gaps in local genomic guidance remain. Strengthening local evidence generation and PGx implementation is essential.

Squirrels (family Sciuridae; hereafter referred to as sciurids) are frequently treated with veterinary medical products, such as fipronil, a topically applied insecticide used for ectoparasite control; however, fundamental information on their drug-metabolizing capacity remains limited. In this study, we examined whether hepatic cytochrome P450 (CYP) profiles and microsomal fipronil metabolism differ among sciurids, Eurasian red squirrel (Sciurus vulgaris orientis), Siberian flying squirrel (Pteromys volans orii), Pallas's squirrel (Callosciurus erythraeus), and laboratory rodents (Mus musculus and Rattus norvegicus). We integrated sequence, expression, and functional analyses with a primary focus on CYP2C and CYP3A, key enzymes involved in xenobiotic metabolism. No clear evidence of sciurid-specific loss or major divergence was detected in CYP2C/3A, and microsomal fipronil metabolic efficiency did not differ significantly among the examined species. RNA sequencing (RNA-Seq) revealed distinct hepatic CYP expression profiles beyond CYP2C/3A; notably, CYP2B represented <1% of total major CYP expression in the Eurasian red squirrel, a proportion lower than that observed in laboratory rodents. These findings provide baseline information on hepatic CYP profiles and microsomal fipronil metabolism in sciurids and may support future comparative studies of wildlife drug metabolism.

The 2023 anthrax outbreak in Zambia, spanning from May to November, resulted in 390 livestock and 39 wildlife fatalities. In addition, 834 suspected human cases and 4 fatalities were recorded. This paper reports the genome sequences of the

Ticks harbor diverse Rickettsia spp., including several spotted fever group rickettsiae of veterinary and public health importance. However, information on tick-associated Rickettsia spp. in Zambia remains geographically limited. In this retrospective molecular survey, we examined 1,587 individual ticks collected from vegetation and domestic animals in eight provinces of Zambia during 2016-2018. Ticks were identified morphologically and screened for Rickettsia spp. by PCR targeting the citrate synthase gene (gltA). Representative gltA positive samples were further characterized by sequencing of ompA, ompB, htrA, sca4, and the 16S rRNA gene. In total, 204 ticks (12.9%) were tested positive for gltA and detected in all eight provinces examined. Sequencing of gltA revealed 26 sequence variants, of which 25 clustered within the spotted fever group and one belonged to transitional group rickettsiae. Multilocus phylogenetic analysis identified sequence variants related to recognized or putative tick-borne rickettsiae, including R. africae, R. conorii, R. massiliae, R. aeschlimannii, Candidatus R. jingxinensis, Candidatus R. rhabdomydis, and R. hoogstraalii. These findings indicate that ticks in Zambia harbor genetically diverse Rickettsia lineages and provide a geographically broad molecular baseline for future surveillance, isolation attempts, and genomic characterization of tick-borne rickettsiae in the region.

Anecdotal accounts of inebriated elephants are widespread across elephant-inhabited regions, yet the molecular and mechanistic basis underlying these observations remains incompletely understood. Alcohol metabolism in mammals is primarily mediated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). We investigated elephant ADH and ALDH at the genomic, transcriptional, and enzymatic levels, comparing them with humans, hamsters, and rats. Elephant liver predominantly expressed three ADH1 genes, as in humans and hamsters that voluntarily consume ethanol, a feature otherwise reported mainly in primates. We measured hepatic ADH and cytosolic ALDH activities in elephants, despite challenges in sample collection. Elephant ADH exhibited high ethanol affinity, allowing enzymatic activity at low substrate concentrations, likely related to large body size. ADH catalytic efficiency was comparable to other species, and cytosolic ALDH showed relatively high efficiency. These results suggest that elephants are less likely to possess exceptionally low hepatic ethanol-metabolizing capacity, although the lack of data on mitochondrial ALDH2 activity should be taken into consideration. Elephants also exhibited unique features, including the absence of ADH4 gene expression, duplication of ALDH1A1, and pseudogenization of ALDH1B1, which appear to have arisen in association with diet and potential functional redundancy among paralogs. In addition to their ecological and evolutionary significance, these findings may contribute to the interpretation of drug metabolism and support evidence-based pharmacological management in elephants, given the role of ADH and ALDH in pharmaceutical metabolism. Together, this study provides a molecular and enzymatic basis for understanding ethanol metabolism in elephants.

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Reproductive dysfunction is a major health concern affecting men and women globally, mediated by the activation of the hypothalamic-pituitary-adrenal axis as well as strongly influenced by exposure to stress. Consequently, this results in suppression of the hypothalamic-pituitary-gonadal (HPG) axis, facilitated by glucocorticoid signalling. Although we have a clear understanding of glucocorticoids as the main mediators of stress-induced reproductive suppression, evidence indicates that monoaminergic pathways, particularly serotonin (5-HT) and its receptors, play pivotal roles in linking stress to reproductive regulation. Kisspeptin neurons have emerged as crucial integrators of both glucocorticoid and serotonergic signals. Current evidence from animal studies demonstrates that stress dysregulates reproductive function at multiple levels of the HPG axis. Glucocorticoids interact through combined genomic and non-genomic pathways to suppress the secretion of kisspeptin, gonadotropin-releasing hormone (GnRH), gonadotropins, as well as gonadal steroidogenesis. In addition to the well-established glucocorticoid mechanisms, monoamines such as 5-HT play a crucial role in mediating the link between stress and reproduction. Recent molecular, electrophysiological, and transcriptomic studies have highlighted the importance of the 5-HT7 receptor, which is highly expressed in kisspeptin neurons of the arcuate nucleus (ARC), where it acts as a critical excitatory driver of GnRH/luteinising hormone (LH) pulse generation. Stress, however, suppresses serotonergic signalling by lowering 5-HT levels and suppressing serotonin receptor expression, including 5-HT7 receptor, thereby reducing kisspeptin and GnRH neuronal excitation. Glucocorticoid-mediated suppression of kisspeptin signalling might be a key underexplored pathway contributing to stress-mediated reproductive dysfunction, particularly when combined with stress-induced reductions in 5-HT and 5-HT receptor expression, suggesting a dual suppressive mechanism. Stress suppresses reproductive function through the coordinated actions of glucocorticoids and monoaminergic, particularly serotonergic, signalling. Kisspeptin neurons situated in the ARC of the hypothalamus act as crucial integrators of glucocorticoid and serotonergic inputs and are particularly susceptible to stress-induced alterations. Normally, serotonin-mediated excitation via the 5-HT7 receptors plays an important role in promoting both kisspeptin and GnRH secretion, which are indispensable for reproductive function. However, stress downregulates 5-HT7 receptor expression in the kisspeptin-producing neurons in the arcuate, leading to the subsequent suppression of GnRH and LH pulsatility. This disruption ultimately results in reproductive dysfunction.