Cathepsin S (CatS) is a proteolytic enzyme and a member of the cysteine protease family of proteolytic enzymes. Cathepsins S, K, and L are particularly similar in terms of their amino acid sequences and interactions with substrates, and this has made it difficult to develop inhibitors with specificity for either CatS, CatK, or CatL. The involvement of CatS in various disease pathophysiologies (autoimmune disorders, cardiovascular diseases, cancer, etc.) has made it a very important target in drug development. Efforts have been made since the early 1990s to develop a specific CatS inhibitor without any major success. Following many failed efforts to develop an inhibitor for CatS, it was discovered that interactions with the amino acid residues at the S2 and S3 pockets of CatS are critical for the identification of CatS-specific inhibitors. Amino acid residues at these pockets have been the target of recent research focused on developing a non-covalent, reversible, and specific CatS inhibitor. Methods applied in the identification of CatS inhibitors include molecular modeling, in-vitro screening, and in-vivo studies. The molecular modeling process has proven to be very successful in the identification of CatS-specific inhibitors, with R05459072 (Hoffmann-La Roche) and LY3000328 (Eli Lilly Company) which has completed phase 1 clinical trials. CatS inhibitors identified from 2011 to 2023 with promising prospects are discussed in this article.

Introduction Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, including adverse outcomes for both the mother and the fetus. Different diagnostic criteria are used for GDM, and it is not clear how these affect the reported prevalence of adverse pregnancy outcomes. This protocol is for a systematic review to describe and compare the prevalence of adverse pregnancy outcomes in GDM using the different diagnostic criteria applied in various countries/regions of the world. Methods and analysis A systematic review and meta-analysis will be carried out. A comprehensive search of observational studies that report the outcomes of interest to this review from 2010 to 2021 will be conducted. We will search the major electronic databases such as PubMed, Scopus, CINHAL and Google Scholar, and screen references of included studies for additional studies. Meta-analyses will be performed, if there is low heterogeneity, and pooled estimates per outcome reported. We will use the bias-adjusted inverse variance heterogeneity model and random effects models, depending on the heterogeneity observed, to pool prevalence estimates and perform subgroup analyses by region, by age group, by diagnostic criteria and by GDM screening method if sufficient data are available. We will also compare the prevalence of adverse outcomes by diagnostic method and report prevalence ratios. We will report 95% confidence estimates for all estimates. Ethics and dissemination Ethical approval is not required as the review uses published data. Findings will be published in peer-reviewed journals and presented at conferences. PROSPERO registration number CRD42020155061.

Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect.

Variation in plant species and extraction solvents play a crucial role in the recovery of their bioactive compounds and antifungal efficacy. Thus, in this study, a comparative investigation was carried out using extraction solvents: 70% acetone and 95% ethanol to obtain crude aqueous extracts from Helichrysum odoratissimum and H. patulum. Crude aqueous extracts were screened using gas chromatography–mass spectrometry (GC–MS), to gain insight into their chemical composition. Phytochemical properties (total polyphenols (TP) and radical scavenging capacity via 2,2-diphenyl-1-picrylhydrazyl (DPPH)), and antifungal activity against Botrytis cinerea of the crude extracts were evaluated. Fungicide (Rovral^® WP) and extraction solvents were used as controls. Variation in Helichrysum spp. and extraction solvent had influence on the chemical composition, phytochemicals, and antifungal activities. Metabolites such as γ-terpinene (≈0.1%), α-amorphene (≈0.6%) α-gurjunene (≈1.4%), β-selinene (2.2–3.2%), γ-gurjunene (≈3.3%), and methyl cinnamate (≈20%) were detected only in extracts of H. patulum. Crude extract of H. odoratissimum using 70% acetone had the highest TP (19.3 ± 0.76 g GA 100 g⁻¹), and DPPH capacity (13,251.5 ± 700.55 µmol Trolox g⁻¹) compared to H. patulum (p ≤ 0.05). Ethanolic extracts of H. patulum showed highest antifungal efficacy (≈65%) against B. cinerea (p ≤ 0.05) compared to other crude extracts. This study showed that Helichrysum spp. differ in their potential as a source for bioactive compounds and antifungal treatments/formulations.