METHODS AND RESULTS: Histopathology revealed increased collagen deposition and altered fiber arrangement in the NP and isoproterenol hydrochloride (ISO) groups compared with the blank group. Systolic and diastolic functions were impaired. Western blotting and qRT-PCR demonstrated that the expression of central myofibrosis-related proteins (collagens Ι and ΙΙΙ, MMP2, MMP9, TGF-β1, α-SMA, IL-1β, and TGF-β1) and genes (Collagen Ι, Collagen ΙΙΙ, TGF-β1, and α-SMA mRNA) was upregulated in the NP and ISO groups compared with the blank group. The mRNA-seq analysis indicated differential expression of TGF-β1 signaling pathway-associated genes and proteins. Fibrosis-related protein and gene expression increased in the CFs stimulated with the recombinant human TGF-β1 and NP, which was consistent with the results of animal experiments. According to the immunofluorescence analysis and western blotting, NP exposure activated the TGF-β1/LIMK1 signaling pathway whose action mechanism in NP-induced CFs was further validated using the LIMK1 inhibitor (BMS-5). The inhibitor modulated the TGF-β1/LIMK1 signaling pathway and suppressed the NP-induced increase in fibrosis-related protein expression in the CFs. Thus, the aforementioned pathway is involved in NP-induced fibrosis.
CONCLUSION: We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-β1/LIMK1 signaling pathway in this process.
OBJECTIVE: Hence, the present review aims to provide an understanding of drinking water (tap water, groundwater, gravity feed system) quality and its potential implications on policy, human health, and drinking water management law and identification of potential direction of future drinking water research and management needs in Malaysia.
METHODS: This study utilized a scoping review method. PRISMA Extension for Scoping Reviews was used for search strategy. Relevant studies were screened using the selected keywords and databases.
RESULTS: A total of 26 drinking water quality studies involving tap water, groundwater, and gravity feed systems have been selected for review. These studies found that the majority of Malaysian Drinking Water and WHO Drinking Water standards have been met. High levels of Cu, Cd, Fe and Pb were attributable to galvanized plumbing and pipe material corrosion. Variation of fluoride in tap water depends on dosage planning and operational processes of the public water supply. Pollutants (nitrate and ammonia) in groundwater and gravity feed system water have been linked to agricultural practices in rural areas. Microbiological quality in tap water is associated with growing biofilms inside the pipelines while in groundwater is caused by shallow surface events. However, only eight studies have reported about the human risks of chemical pollutants in tap water.
IMPACT STATEMENT: The review discusses the state of drinking water quality in Malaysia and its impact on public health. It suggests that policymakers can use this information to improve the quality of drinking water and enforce restrictions, while also raising public awareness about the importance of safe drinking water. The study can guide future research and initiatives in Malaysia, ultimately contributing to efforts to ensure access to clean and dependable drinking water.