Introduction: Epithelial–mesenchymal transition (EMT) and overexpression of drug efflux transporters have been reported to cause doxorubicin resistance. Our previous study indicated that TMEPAI (transmembrane prostate androgen-induced protein) attenuated doxorubicin sensitivity in triple-negative breast cancer cells. However, how TMEPAI contributes to doxorubicin resistance in TNBC remains unclear. Thus, the present study aimed to elucidate the mechanism of TMEPAI in doxorubicin resistance in triple-negative breast cancer cells. Methods: We used BT549, triple-negative cells wild type (WT), and BT549 TMEPAI knock-out. Both cells were treated with TGF-β 2 ng/mL for 24 hours, followed by TGF-β 2 ng/mL and doxorubicin 12.9 nM for another 24 hours. Afterward, the cells were harvested and counted. Cells were further lysed and used for RT-PCR and Western blot analysis. We determined the expression levels of proliferation, apoptosis, EMT markers, and drug efflux transporters. Additionally, we investigated the expressions of PI3K as well as SMAD3 and AKT phosphorylation. Results: TNBC cells were shown to be less sensitive to doxorubicin in the presence of TMEPAI. TMEPAI was shown to alleviate the mRNA expressions of apoptosis markers: Bax, Bcl2, Caspase-3, and Caspase-9. Our results indicated that the presence of TMEPAI greatly amplifies EMT and increases drug efflux transporter expressions after doxorubicin treatment. Furthermore, our findings demonstrated that TMEPAI reduced the action of doxorubicin in inhibiting SMAD3 phosphorylation. TMEPAI was also shown to modify the effect of doxorubicin by reducing PI3K expressions and Akt phosphorylation in triple-negative breast cancer cells. Conclusion: Our findings indicate that TMEPAI promotes EMT and drug efflux transporters at least in part by shifting doxorubicin action from SMAD3 phosphorylation reduction to PI3K/AKT inhibition in triple-negative breast cancer cells.

Purpose: Triple-negative breast cancer (TNBC) is a refractory type of breast cancer with poor prognosis and limited choice for treatment. Previous studies had shown that TNBC has high expressions of transmembrane prostate androgen-induced protein (TMEPAI). TMEPAI was known to be induced by TGF-β/Smad signaling and have tumorigenic functions that converting TGF-β from tumor suppressor to tumor promoter and inducing epithelial–mesenchymal transition (EMT). Therefore, we aimed to define the role of TMEPAI in triple-negative breast cancer cells treatment using several anti-cancers in the presence of TGF-β. Methods: TMEPAI-knock out (KO) was carried out in a triple-negative breast cancer cell, BT549. TMEPAI editing was developed using the CRISPR-Cas9 system using two combinations of sgRNA to remove exon 4 of the TMEPAI gene entirely. Genotyping and proteomic analysis were performed to check the establishment of the TMEPAI-KO cells. Wild type (WT) and KO cells were used to determine inhibitory concentration 50% (IC ₅₀) of several anti-cancers: doxorubicin, cisplatin, paclitaxel, and bicalutamide in the presence of TGF-β treatment. Results: KO cells were successfully established by completely removing the TMEPAI gene, which was proven in genomic and proteomic analysis. Further, in TMEPAI-KO cells, we found a significant reduction of IC ₅₀ for doxorubicin and paclitaxel, and minimal effects were seen for cisplatin and bicalutamide. Our findings suggest that TGF-β-induced TMEPAI attenuates the response of TNBC to doxorubicin and paclitaxel, but not to cisplatin and bicalutamide. Conclusion: TGF-β induced TMEPAI contributes to the reduced response of TNBC treatment to doxorubicin and paclitaxel, but minimal on cisplatin and bicalutamide. Further study is needed to confirm our findings in other growth factor-induced cells, as well as in in vivo model.

Aging is a natural skin process that occurs due to intrinsic and extrinsic factors, such as excessive exposure to ultraviolet light (photoaging). The mechanism of damage involves the production of excess free radicals that trigger oxidative stress in the skin. Determining the natural products that have high antioxidant activities as antiaging is up most important. Cinnamomum burmannii and Michelia champaca are typical Aceh plants that are believed to have high antioxidant effects. The aim of this study was to determining the contents of C. burmannii and M. champaca as well as to determine the antioxidant and antiaging activities of either individually or combinations. The qualitative phytochemical and semi-quantitative analysis of the extracts were conducted using gas chromatography and mass spectroscopy (GC-MS). The antioxidant activity was examined by radical scavenging using the DPPH radical while the antiaging activity was tested the tyrosinase enzyme inhibition test. The phenolic and flavonoid contents of C. burmannii were higher than M. champaca (66.34 vs 24.71 mg gallic acid equivalent/gr) and (80.52 vs 60.20 mg quercetin equivalent/gr). The inhibitory concentration (IC₅₀) of M. champaca extract in inhibiting DPPH indicated that M. champaca had a better antioxidant activity than C. burmannii. The combination of C. burmannii and M. champaca extracts had a lower IC₅₀ compared to M. champaca alone. C. burmannii and M. champaca extract had a weak potential to inhibit tyrosinase activity (IC₅₀ value ≥1000 µg/mL). In conclusion, this study indicates that M. champaca and C. burmannii have strong antioxidant activities and these might associate with polyphenol contents.

Background and Aim: Bluetongue (BT) is an economically important viral disease of domestic and wild ruminants, caused by the bluetongue virus (BTV), and transmitted primarily by Culicoides midges. The virus has at least 28 known serotypes and several emerg­ing strains, with its distribution expanding beyond traditional endemic zones due to climate change and global trade. This review summarizes recent developments in the epidemiology, molecular characterization, diagnostics, vaccines, and con­trol of BT, with an emphasis on its implications within the One Health framework. A comprehensive literature search cov­ering studies from 2000 to 2025 revealed significant outbreaks in Europe (2024–2025) involving BTV-3 and BTV-12, as well as the emergence of novel serotypes in Asia and Africa. Global economic losses exceed USD 3 billion annually due to mortality, production losses, and trade restrictions. Advances in molecular diagnostics, such as reverse transcription polymerase chain reaction, whole-genome sequencing, and rapid field assays like loop-mediated isothermal amplification and clustered regularly interspaced short palindromic repeats -based platforms, have improved surveillance and serotype identification. Although vaccination remains the cornerstone of BT control, current live and inactivated vaccines are lim­ited by serotype specificity and reassortment risks, highlighting the need for new-generation virus-like particle, recombi­nant, DNA, and mRNA-based vaccines. Persistent challenges include the absence of differentiating infected from vaccinated animals -compatible polyvalent vaccines, incomplete knowledge of wildlife reservoirs, and uneven surveillance capacities worldwide. Strengthening integrated vector management, genomic monitoring, and climate-informed control strategies through a coordinated One Health approach will be vital to reduce the global burden of bluetongue. Keywords: bluetongue virus, Culicoides vectors, diagnostics, epidemiology, livestock disease control, One Health, vaccination.

Background and Aim: Legionnaires’ disease (LD), caused by the Gram-negative bacterium Legionella pneumophila, has emerged as a significant public health concern due to its rising incidence and high morbidity and mortality rates. This review comprehensively examines the etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prevention of LD. The bacterium thrives in aquatic environments, often within biofilms and protozoan hosts, contributing to its resilience and widespread distribution in natural and man-made water systems. Transmission primarily occurs through the inhalation of contaminated aerosols, with immunocompromised individuals, the elderly, and smokers being at heightened risk. Clinically, LD presents as a severe pneumonia with systemic involvement, and its diagnosis often relies on culture, urinary antigen tests, and molecular methods. The treatment landscape is dominated by macrolides and fluoroquinolones, with emerging research into alternative therapies to combat antimicrobial resistance. Effective public health strategies, including rigorous water management practices and infection control measures, are vital in mitigating the risk of outbreaks. This review aims to enhance clinical awareness and inform public health initiatives by elucidating the complex interplay between bacterial virulence, host factors, and environmental conditions that contribute to LD transmission and persistence. A better understanding of these dynamics is crucial for developing robust prevention and control strategies, ultimately reducing the global burden of this potentially life-threatening disease. Keywords: Legionella pneumophila, Legionnaires’ disease, pneumonia, public health, waterborne pathogens.

Nephrotoxicity is the most common side effect of gentamicin, an aminoglycoside antibiotic group. It was mediated by oxidative stress mechanisms. Abelmoschus manihot L. leaves (AML) have antioxidant activity flavonoids. This study aims to determine the nephroprotective effect of AML in gentamicin-induced nephrotoxicity using mice models. It conducted an experimental design study in a pharmacology laboratory using mice models. It was conducted experimentally in 7 groups. There are normal, solvent, negative control, and four test groups (given an ethanolic extract of AML at doses of 50, 100, 200, and 400 mg/kgBW) which were administered orally for 7 days. Gentamicin 112 mg/kgBW was induced intraperitoneally ^on the 8th day. All mice were anesthetized on the 11^th day to collect blood serum and renal organs for further examination. The data were analyzed using SPSS version 26 for One Way ANOVA test and followed by Duncan's post-hoc analysis test. The difference is considered significant if the p-value <0.05. Gentamicin successfully induced renal damage based on increasing creatinine and blood urea nitrogen (BUN) levels. This was by histopathology analysis which showed renal necrosis in the negative control group. Ethanolic extract of AML prevents nephrotoxicity due to gentamicin in a dose-dependent manner in creatinine level but not in BUN and histopathology. However, taken together all results showed that ethanol extract of AML has a nephroprotective effect in gentamicin-induced nephrotoxicity. Keywords: Abelmoschus manihot L., gentamicin, nephroprotection, renal histopathology