An Overview of Hepatitis C Virus and Liver Cirrhosis in Pakistan

ULLAH, A; BIBI, A; ULLAH, I; KAYANI, REZ; ASIM, M; MUNAWAR, N; AMJAD, M; SIRAJ, M; GOHAR, M; KHAN, MA

doi:10.54112/bbasr.v2024i1.64

Cited by 3 publications

(1 citation statement)

References 93 publications

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“…The NBDs interact with ATP, and the R domain interacts with NBD1, separating the two TMDs [ 11 , 12 ]. The CFTR protein is expressed in the apical membranes of polarized epithelial cells in the sweat ducts, pancreatic duct, intestines, biliary tree, and vas deferens, and a few non-epithelial containing tissues such as erythrocytes, cardiac myocytes, immune cells such as macrophages, and smooth muscle [ 13 , 14 , 15 , 16 , 17 , 18 ]. The domains of the CFTR protein are aligned and arranged in a way to form a pore that selectively allows for the movement of anions [ 16 ].…”

Section: Structure and Function Of Cftrmentioning

confidence: 99%

Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies

Anwar,

Peng,

Zahid

et al. 2024

ARM

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A common life-threatening hereditary disease, Cystic Fibrosis (CF), affects primarily Caucasian infants. High sweat-salt levels are observed as a result of a single autosomal mutation in chromosome 7 that affects the critical function of the cystic fibrosis transmembrane regulator (CFTR). For establishing tailored treatment strategies, it is important to understand the broad range of CFTR mutations and their impacts on disease pathophysiology. This study thoroughly investigates the six main classes of classification of CFTR mutations based on their functional effects. Each class is distinguished by distinct molecular flaws, such as poor protein synthesis, misfolding, gating defects, conduction defects, and decreased CFTR expression at the apical membrane. Furthermore, this paper focuses on the emerging field of CFTR modulators, which intend to restore CFTR function or mitigate its consequences. These modulators, which are characterized by the mode of action and targeted mutation class, have the potential to provide personalized therapy regimens in CF patients. This review provides valuable insights into the genetic basis of CF pathology, and highlights the potential for precision medicine methods in CF therapy by thoroughly investigating CFTR mutation classification and related modulators.

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Section: Structure and Function Of Cftrmentioning

confidence: 99%

Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies

Anwar,

Peng,

Zahid

et al. 2024

ARM

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GC–MS analysis, molecular docking, and apoptotic-based cytotoxic effect of Caladium lindenii Madison extracts toward the HeLa cervical cancer cell line

Kalsoom,

Altaf,

Sarwar

et al. 2024

Sci Rep

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Utilizing medicinal plants and other natural resources to prevent different types of human cancers is the prime focus of attention. Cervical cancer in women ranks as the fourth most common type of malignancy. The current study used gas chromatography-mass spectrometry (GC-MS) to identify the active phytochemical constituents from Caladium lindenii leaf extracts using ethanol (ECL) and n-hexane (HCL) solvents. Plant extracts were tested for potential cytotoxic effects on HeLa and HEK-293 T cells using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and the crystal violet assays. SYBR Green-based real-time PCR was performed to assess the mRNA expression profile of the apoptosis biomarkers (BCL-2 and TP53). The molecular interaction of the compounds with the targeted proteins (TP53, BCL2, EGFR, and HER2) was determined using molecular docking. GC-MS analysis revealed a total of 93 compounds in both extracts. The ECL extract significantly reduced the proliferation of HeLa cervical cancer cells, with an IC 50 value of 40 µg/mL, while HEK-293 T cells showed less effect (IC 50 = 226 µg/mL). The quantitative RT-PCR gene expression analysis demonstrated the ethanol extract regulated TP53 and BCL2 mRNA expressions in treated cancer cell samples. Heptanediamide, N,Nʹ-di-benzoyloxy-(− 10.1) is the best-docked ligand with a TP53 target found in the molecular docking study, whereas EGFR/Clionasterol had the second highest binding affinity (− 9.7), followed by EGFR/Cycloeucalenol (− 9.6). It is concluded that ECL extract has promising anti-cervical cancer potential and might be valued for developing new plant-derived anticancer agents after further investigations.

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Silibinins and curcumin as promising ligands against mutant cystic fibrosis transmembrane regulator protein

Akram,

Sakhawat,

Ghani

et al. 2024

AMB Expr

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Cystic Fibrosis Transmembrane Regulator (CFTR) is a significant protein that is responsible for the movement of ions across cell membranes. The cystic fibrosis (CF) occur due to the mutations in the CFTR gene as it produces the dysfunctional CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands selection was performed through virtual screening and top 3 ligands choose out of 65 ligands silibinins, curcumin, demethoxycurcumin were selected with a reference drug Trikafta (R*). According to docking, ADMET analyses, the natural ligands (Silibinins and Curcumin) displayed best binding energy, pharmacokinetic and free toxicity than other natural compounds and reference drug (R*). An MD simulation for 200 ns was also established to ensure that natural ligands (Silibinins and Curcumin) attached to the target protein favorably and dynamically, and that protein–ligand complex stability was maintained. It is concluded that silibinins and curcumins have a better capacity to decrease the effect of mutant CFTR protein through improved trafficking and the restoration of original function. In conclusion, in silico studies demonstrate the potential of silibinins and curcumin as therapeutic agents for cystic fibrosis, particularly for the D614G mutated protein. Their ability to increase CFTR function while reducing cellular stress and inflammation, together with their favorable safety profile and accessibility could make them valuable additions to cystic fibrosis treatment options. Further experimental and clinical validation will be required to fully realize their potential and include them into effective therapy regimens.

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An Overview of Hepatitis C Virus and Liver Cirrhosis in Pakistan

Cited by 3 publications

References 93 publications

Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies

Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies

GC–MS analysis, molecular docking, and apoptotic-based cytotoxic effect of Caladium lindenii Madison extracts toward the HeLa cervical cancer cell line

Silibinins and curcumin as promising ligands against mutant cystic fibrosis transmembrane regulator protein

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