A major obstacle in treating malaria is the emergence of antimalarial drug resistance. The aminoacyl-tRNA synthetases (aaRSs), which are essential enzymes for protein synthesis, have been identified as potential targets for the discovery of anti-parasitic drugs. Of these, Glutamyl-tRNA synthetase (GluRS) is a crucial aaRS enzyme in Plasmodium falciparum and is a vital therapeutic target. In this study, potential GluRS inhibitors are reported from the Medicinal Fungi Secondary Metabolites and Therapeutics (MeFSAT) chemical library using structure based virtual screening via PyRx v0.8. To evaluate the stability of top hit protein-inhibitor complexes, molecular dynamics simulations (time period, 100 ns) were performed from an initial batch of 1,830 compounds. The two shortlisted compounds, MSID000152 and MSID000974, showed the strongest negative binding affinities of −10.4 kcal/mol and −10.1 kcal/mol, respectively. For comparative analysis, Chloroquine was used as a control to validate the screening results. The dynamics of both complexes showed stable structure, with mean RMSD of 3.94 Å for MSID000152, 2.35 Å for MSID000974, and 2.39 Å for chloroquine. The MSID000152 illustrated favorable MMPB/GBSA binding free energy. Taken together, the study highlights MSID000152 and MSID000974 as promising antimalarial lead compounds for additional in vitro and in vivo investigations.

In brief: Protein phosphatase 1 catalytic subunit gamma isoform 2 (PP1γ2) is a unique phosphatase expressed only in mammalian testes and sperm cells. The PP1γ2 isoform is indispensable for sperm motility and fertility and cannot be replaced by the PP1γ1 isoform for these functions. The serine–threonine phosphatase has four paralogs – PP1α, PP1β, PP1γ1 and PP1γ2 – encoded by three genes, Ppp1ca , Ppp1cb and Ppp1cc . Protein phosphatase PP1γ2, one of two isoforms of the gene Ppp1cc , is expressed in spermatogenic cells in the testes and sperm, while PP1γ1 is found in somatic cells. The two PP1γ isoforms, formed by alternate splicing that occurs only in mammals, are identical except at their C-termini. Global or testis-specific knockout of Ppp1cc in mice results in male infertility due to disrupted spermiation and mid-to-late spermiogenesis. Transgenic expression of PP1γ2, driven by a testis-specific promoter in differentiating spermatogenic cells, rescues spermatogenesis and fertility in the Ppp1cc -null mice. Why PP1γ2 is essential and present only in mammalian sperm is a mystery. We have generated a knock-in mouse where the Ppp1cc gene is edited to express only PP1γ1. Spermatogenesis was normal in knock-in mice. Testis-expressed PP1γ1 in the knock-in mice and PP1γ2 in the wild-type mice were incorporated in equal amounts into sperm. Sperm bearing PP1γ1 have reduced flagellar beat amplitude and motility, and male mice were severely sub-fertile. Although in the wild-type mice, PP1γ2 is present in both the head and tail, in the knock-in mice, PP1γ1 is absent in sperm heads, leading to an altered intra-sperm protein phosphatase landscape. Phosphoproteomic analysis of sperm proteins suggested a plausible molecular basis for compromised PP1γ1 functions: it identified GSK3α, a known substrate of PP1, to be dysregulated in knock-in sperm. This study provides a preliminary explanation for the isoform-specific requirement of PP1γ2 for male fertility.

Background: Iron deficiency anemia (IDA) represents a significant public health concern, particularly among female populations. Various demographic factors, including age and socioeconomic status, have a substantial impact on overall health outcomes, contributing to the prevalence of IDA. The primary objective of this study was to assess the knowledge and awareness of iron deficiency anemia among the adult population and to examine its correlation with various sociodemographic factors. Methods: A cross-sectional study was conducted in the Northern Region of Saudi Arabia between October and December 2024. Data were collected using a structured questionnaire from 385 participants aged 18 years and older. The Chi-square test was utilized to assess the association between categorical variables. Results: In this study, 42.5% of participants demonstrated good knowledge of IDA, 48.1% had moderate knowledge, and 9.4% showed poor knowledge. Knowledge levels were significantly associated with gender, age, education, and self-perceived IDA status. Women, older individuals, and those with higher levels of education had a greater knowledge of IDA. Regarding attitude, 93% of participants had a positive attitude, while only 7% exhibited a negative attitude. Interestingly, none of the explanatory variables were significantly linked to attitude, suggesting that positive attitude toward IDA was consistent across all demographic groups. Conclusions: This study highlights the need for targeted health initiatives focusing on diet, supplementation, symptom recognition, and prevention to effectively reduce the burden of IDA. Prioritizing education through symposiums and medical programs in high-prevalence regions is crucial.