Phenylethanoid glycosides (PhGs) are water-soluble natural compounds widely distributed in the plant kingdom, attracting significant attention from medicinal chemists due to their promising potential in pharmaceutical applications. PhGs exhibit a broad range of activities, including neuroprotective, hepatoprotective, anti-inflammatory, antioxidant, and immunomodulatory effects. This review aims to update the hepatoprotective effects of total PhG extracts and individual PhG compounds, as well as the underlying mechanisms. Additionally, we describe the structural characteristics, representative PhG compounds, and their structure–activity relationships. In brief, total PhG extracts can exert synergistic protection by reducing serum alanine aminotransferase/aspartate aminotransferase levels, suppressing oxidative stress, and attenuating inflammatory responses. Representative PhGs, including acteoside (verbascoside), echinacoside, forsythoside A (also known as forsythiaside A), and cistanoside A, protect against liver injury through modulation of the Nrf2/HO-1, NF-κB, MAPK, and TGF-β/Smad pathways, thereby regulating oxidative stress, inflammation, apoptosis, fibrosis, and lipid metabolism. Structurally, PhGs consist of a phenylethyl alcohol core, cinnamoyl residues, and glycosyl moieties. Structure–activity relationship analyses indicate that caffeoyl substitution, multiple phenolic hydroxyl groups, and optimal glycosylation patterns are key determinants of hepatoprotective efficacy.

Liver fibrosis is characterized by the excessive deposition of extracellular matrix, a process primarily driven by activated hepatic stellate cells (HSCs), and currently lacks effective therapy. Cathepsin K (CTSK) exhibits context-dependent roles across organ systems in fibrosis, but its function in liver fibrosis is unclear. This study aimed to investigate the role and underlying mechanisms of CTSK during liver fibrosis.

CTSK expression was analyzed in human fibrotic liver samples via transcriptomic analysis and confirmed in murine fibrosis models. The function of CTSK was investigated in both primary HSCs and LX-2 cells by assessing its effects on cell activation, proliferation, apoptosis, and the underlying signaling pathways following CTSK overexpression. The therapeutic potential was evaluated using an adeno-associated virus serotype 8 to overexpress CTSK in two etiologically distinct murine fibrosis models.

CTSK was upregulated in activated HSCs and fibrotic livers. Furthermore, we discovered that it mediates a negative feedback loop to inhibit the TGF-β/Smad pathway via Smad7/Smurf2-dependent TGF-β receptor-I degradation, thereby suppressing HSC activation and proliferation. CTSK also induced mitochondrial apoptosis through Bax/Bcl-2 imbalance and caspase-3 activation. Together, these actions contribute to the anti-fibrotic effect of CTSK. Notably, adeno-associated virus serotype 8-mediated CTSK overexpression attenuated liver fibrosis across multiple murine models.

Our study demonstrates that elevated CTSK functions as an endogenous protective factor that attenuates liver fibrosis. CTSK mediates negative feedback inhibition of the TGF-β pathway while concurrently promoting the mitochondrial apoptosis pathway. The dual anti-fibrotic mechanisms identify CTSK as a promising therapeutic target for liver fibrosis.

Cervical cancer, driven mainly by persistent high-risk human papillomavirus infection, remains a major public health problem in Bangladesh, with 9,640 new cases and 5,826 deaths in 2022. Early detection of pre-cancerous cervical lesions (PCL) is essential, yet limited evidence exists on factors associated with PCL among Bangladeshi women. This study aimed to identify factors associated with PCL among women attending cervical cancer screening centers at selected tertiary hospitals.

An age-matched (±5 years) case-control study was conducted in two tertiary hospitals. Cases were women who tested colposcopy-positive for PCL, and controls were visual inspection with acetic acid-negative women attending the same screening centers. A total of 38 cases and 76 controls were included. Data were collected through face-to-face interviews using a structured questionnaire. Multivariable logistic regression identified factors associated with PCL, with significance set at p < 0.05.

A history of sexually transmitted infections (adjusted odds ratio (AOR) = 36.73; 95% confidence interval (CI): 3.25–414.83), pelvic infections (AOR = 6.48; 95% CI: 1.24–33.85), not living with a husband (AOR = 4.48; 95% CI: 1.06–18.90), and overweight/obesity (AOR = 3.58; 95% CI: 1.14–11.22) were significantly associated with higher odds of PCL. Menstrual irregularity, genital ulcer history, and number of lifetime sexual partners showed no significant association.

Sexually transmitted infections, pelvic infections, overweight/obesity, and not living with husband were identified as factors associated with PCL. Strengthened infection prevention, lifestyle counseling, and targeted health education may support ongoing cervical cancer prevention efforts in Bangladesh.

Chaperone-like proteins are involved in the pathogenesis of coronavirus infection through regulation of the viral life cycle, immune response, and antigen presentation. A recently discovered class of chaperones, called heat-resistant obscure proteins (Hero proteins), performs functions similar to other molecular chaperones. This study aimed to investigate the association between the gene encoding the Hero protein SERF2 (Hero7) and the risk of severe COVID-19.

This case-control study was conducted according to the STROBE protocol. A total of 1,373 unrelated Russians (178 patients with severe COVID-19 and 1,195 controls) were recruited. Genotyping of rs4644832 in the SERF2 gene was performed using a probe-based polymerase chain reaction approach. The effects of the single nucleotide polymorphisms (SNPs) were analyzed using bioinformatics tools, including GTExPortal, eQTLGen, HaploReg, atSNP, Gene Ontology, Lung Disease and Common Metabolic Diseases Knowledge Portals, and the STRING database.

SNP rs4644832 in the SERF2 gene (effect allele G) was associated with a decreased risk of severe COVID-19 in the total sample (odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.39–0.81, P = 0.001), females (OR = 0.51, 95% CI 0.31–0.87, P = 0.006), non-smokers (OR = 0.46, 95% CI 0.29–0.74, P = 0.0004), individuals with body mass index ≥ 25 (OR = 0.42, 95% CI 0.25–0.7, P = 0.0004), individuals with low fruit and vegetable intake (OR = 0.38, 95% CI 0.22–0.67, P = 0.0004), and individuals with low physical activity (OR = 0.41, 95% CI 0.23–0.75, P = 0.002).

The G allele of rs4644832 in the SERF2 gene appears to have a protective effect against severe COVID-19. Functional annotation of rs4644832 suggests that it may influence COVID-19 pathogenesis through regulation of proteostasis, ubiquitination, inflammation-induced protein aggregation, the viral life cycle, and cytoskeletal functions.

Infectious diarrhea is a gastrointestinal illness that results in around 1.7 billion cases and 525,000 deaths annually, particularly among children under five, according to the World Health Organization. While some Cameroonian medicinal plants show promise for treating diarrhea, many plants are used without established scientific evidence of their efficacy. These plants include Tithonia diversifolia (T. diversifolia) and Solanum torvum (S. torvum), which are traditionally used to treat diarrheal symptoms. This study sought to investigate the anti-Shigella activity of leaf extracts from T. diversifolia and S. torvum.

Extracts from T. diversifolia and S. torvum were obtained by successive maceration in solvents of increasing polarity, including hexane, dichloromethane, ethyl acetate, methanol, and water. The as-prepared extracts (10) were evaluated for antibacterial activity against selected Shigella species using an in vitro experiment. The mode of action of the bioactive extracts was determined in Shigella through growth kinetic analysis.

Hexane extract from S. torvum (St-HEX-F) and dichloromethane extract from T. diversifolia (Td-DCM-F) inhibited the growth of Shigella flexneri NR-518 and Shigella boydii NR-521 with minimum inhibitory concentration (MIC) values of 500 and 1,000 µg/mL, respectively. Shigella flexneri and Shigella boydii were the most sensitive strains, whereas Shigella sonnei was the most resistant strain. Bacterial growth kinetics revealed that St-HEX-F and Td-DCM-F are bacteriostatic at MIC and bactericidal at 2×MIC and 4×MIC.

Extracts from T. diversifolia and S. torvum possess anti-Shigella activity and could be used as a potential source of active ingredients for developing new treatments against diarrhea caused by multidrug-resistant Shigella.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for effective therapies. Although miR-125b-5p shows therapeutic potential, its efficacy in metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC and the underlying mechanisms remain unclear. In this study, we aimed to develop a magnetic resonance imaging (MRI)-trackable miR-125b-5p-engineered MSC platform for HCC therapy and to determine whether MASLD attenuates its antitumor efficacy through metabolic reprogramming.

Bone marrow mesenchymal stem cells (MSCs) were genetically engineered to coexpress miR-125b-5p (a therapeutic gene) and ferritin heavy chain (Fth; a MRI reporter gene), enabling sustained delivery and real-time tracking. Orthotopic HCC models with or without MASLD were established to evaluate therapeutic outcomes. In vivo MRI, histological analyses, and bioinformatics approaches were used to assess efficacy and mechanisms.

Transplantation of miR-125b-5p-Fth-MSCs significantly suppressed HCC growth in vivo over an extended period. However, MASLD attenuated this therapeutic effect. Mechanistically, miR-125b-5p directly targeted hexokinase 2 (HK2), inhibiting HCC proliferation and migration through suppression of the PI3K/AKT/mTOR pathway. Fatty acid-induced lipotoxicity upregulated HK2 expression and counteracted the antitumor effects of miR-125b-5p.

Multigene-modified MSCs enable effective, MRI-monitored HCC therapy. MASLD diminishes the efficacy of miR-125b-5p through HK2 upregulation. These findings establish a multimodal theranostic framework for HCC and provide mechanistic insights into MASLD-associated therapeutic resistance.