Biomedical subjects

Akbar Ali

Publications and source records attributed to Akbar Ali.

7 recordsLinked to original sources

PubMed2025

Comprehensive transcriptomic analysis of myostatin-knockout pigs: insights into muscle growth and lipid metabolism.

Pigs are a vital source of protein worldwide, contributing approximately 43% of global meat production. Recent genetic advancements in the myostatin (MSTN) gene have facilitated the development of double-muscling traits in livestock. In this study, we investigate the transcriptomic profiles of second-generation MSTN-knockout (MSTN-/-) pigs, generated through CRISPR/Cas9 gene editing and somatic cell nuclear transfer (SCNT). Using RNA sequencing, we compared the transcriptomic landscapes of muscle tissues from MSTN-/- pigs and wild-type (WT) counterparts. The sequencing yielded an average unique read mapping rate of 86.7% to the Sus scrofa reference genome. Our analysis revealed 15,142 differentially expressed genes (DEGs), including 121 novel genes, with 2554 genes upregulated and 1629 downregulated in the MSTN-/- group relative to the wild-type group. Notable transcriptomic changes were identified in genes associated with muscle development, lipid metabolism, and other physiological processes. These findings provide valuable insights into the molecular consequences of MSTN inactivation, with potential applications in the optimization of livestock breeding and advancements in biomedical research.

Animals↗

PubMed2007

Primary gastric lymphoma.

OBJECTIVE: To evaluate the clinico-pathological status of Primary Gastric Lymphoma (PGL) at presentation in King Fahad Hospital, Madina Munawra, Kingdom of Saudi Arabia (KSA). STUDY DESIGN: A case series. PLACE AND DURATION OF SUDY: Oncology Department of King Fahad Hospital, Madina Munawra, KSA, from 1990 to 1998. PATIENTS AND METHODS: Case records of 22 patients with a histologically-confirmed diagnosis of PGL were analyzed. Tumors were staged according to the Ann Arbor Classification and divided according to the Rappaport working formulation. According to the treatment modality, different groups were established. Any other histopathological type was excluded from the study. Data were analyzed by frequency calculations. Survival was calculated from the date of surgery. RESULTS: All cases were Non-Hodgkin Lymphoma (NHL). The peak age was in the sixth decades with a slight male preponderance. Most common presenting symptoms were epigastric or upper abdominal pain with or without mass. There were 10 (45%) patients with stage II, and 6 (27%) patients each with stage III and IV diseases. Diffuse large cell lymphoma was found in 12 (55%), poorly differentiated lymphoma in 3 (14%) and diffuse mixed in 7 (32%). Helicobacter pylori infection was found in 2 (9%). Sixteen (73%) patients underwent chemotherapy with some surgical resection, in 5 (23%) surgical procedure was palliative bypass and 11 (50%) had partial gastrectomy. Three (14%) had only chemotherapy after endoscopic biopsy. Two (9%) patients needed urgent surgical intervention. One (5%) patient had total gastrectomy followed by radiotherapy. Eleven (50%) had more than 3 years survival. CONCLUSION: PGL is usually of NHL type, presenting in the sixth decade, and can be successfully treated with both surgery and chemotherapy when patients presented at stage II. Chemotherapy after sub-total gastrectomy or biopsy was the best treatment option.

Abdominal Pain↗

PubMed2006

Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands.

Here, we describe the design, synthesis, and biological evaluation of novel HIV-1 protease inhibitors incorporating N-phenyloxazolidinone-5-carboxamides into the (hydroxyethylamino)sulfonamide scaffold as P2 ligands. Series of inhibitors with variations at the P2 phenyloxazolidinone and the P2' phenylsulfonamide moieties were synthesized. Compounds with the (S)-enantiomer of substituted phenyloxazolidinones at P2 show highly potent inhibitory activities against HIV-1 protease. The inhibitors possessing 3-acetyl, 4-acetyl, and 3-trifluoromethyl groups at the phenyl ring of the oxazolidinone fragment are the most potent in each series, with K(i) values in the low picomolar (pM) range. The electron-donating groups 4-methoxy and 1,3-dioxolane are preferred at P2' phenyl ring, as compounds with other substitutions show lower binding affinities. Attempts to replace the isobutyl group at P1' with small cyclic moieties caused significant loss of affinities in the resulting compounds. Crystal structure analysis of the two most potent inhibitors in complex with the HIV-1 protease provided valuable information on the interactions between the inhibitor and the protease enzyme. In both inhibitor - enzyme complexes, the carbonyl group of the oxazolidinone ring makes hydrogenbond interactions with relatively conserved Asp29 residue of the protease. Potent inhibitors from each series incorporating various phenyloxazolidinone based P2 ligands were selected and their activities against a panel of multidrug-resistant (MDR) protease variants were determined. Interestingly, the most potent protease inhibitor starts out with extremely tight affinity for the wild-type enzyme (K(i) = 0.8 pM), and even against the MDR variants it retains picomolar to low nanomolar K(i), which is highly comparable with the best FDA-approved protease inhibitors.

Amides↗

PubMed2005

Dissecting RNA-interference pathway with small molecules.

RNA interference (RNAi) is a process whereby short-interfering RNAs (siRNA) silence gene expression in a sequence-specific manner. We have screened a chemical library of substituted dihydropteridinones and identified a nontoxic, cell permeable, and reversible inhibitor of the RNAi pathway in human cells. Biochemical and fluorescence resonance-energy transfer experiments demonstrated that one of the compounds, named ATPA-18, inhibited siRNA unwinding that occurred within 6 hr of siRNA transfection. Extracts prepared from ATPA-18-treated cells also exhibited a decrease in target RNA cleavage by activated RNA-induced silencing complex (RISC*). Interestingly, when activated RISC*, which harbors unwound antisense siRNA, was treated with ATPA-18 in vitro, target RNA cleavage was not affected, indicating that this compound inhibited siRNA unwinding or steps upstream of unwinding in the RNAi pathway. Our results also establish the timing of siRNA unwinding and show that siRNA helicase activity is required for RNAi. ATPA-18 analogs will therefore provide a new class of small molecules for studying RNAi mechanisms in a variety of model organisms and deciphering in vivo genetic functions through reverse genetics.

Cell Line↗

PubMed2004

Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells.

RNA interference (RNAi) is the process by which short-interfering RNA (siRNA) target a specific mRNA for degradation through interactions with an RNA-induced silencing complex (RISC). Here, a clear correlation between siRNA localization, cellular uptake, and RNAi activity was discovered by delivering siRNA into cells using siRNA-TAT(47-57) peptide, siRNA-TAT(47-57)-derived oligocarbamate conjugates, or nanoparticles. For successful RNAi, the localization of siRNA was distinctly perinuclear, suggesting that siRNA is targeted to these regions for interactions with RISC to induce RNAi. siRNA sequence variation and the presence of the target mRNA apparently did not change the subcellular localization pattern of siRNA. Intriguingly, siRNA conjugated to TAT(47-57) peptide or TAT(47-57)-derived oligocarbamate resulted in efficient RNAi activity and perinuclear localization of siRNA that was distinctly different from nonconjugated free TAT peptide nucleolar localization. These results suggest that interactions with RISC dictate siRNA localization even when siRNA is conjugated to TAT(47-57) peptide.

Base Sequence↗

PubMed2003

Discovery of a small molecule Tat-trans-activation-responsive RNA antagonist that potently inhibits human immunodeficiency virus-1 replication.

Antiretroviral therapy to treat AIDS uses molecules that target the reverse transcriptase and protease enzymes of human immunodeficiency virus, type 1 (HIV-1). A major problem associated with these treatments, however, is the emergence of drug-resistant strains. Thus, there is a compelling need to find drugs against other viral targets. One such target is the interaction between Tat, an HIV-1 regulatory protein essential for viral replication, and trans-activation-responsive (TAR) RNA. Here we describe the design and synthesis of an encoded combinatorial library containing 39,304 unnatural small molecules. Using a rapid high through-put screening technology, we identified 59 compounds. Structure-activity relationship studies led to the synthesis of 19 compounds that bind TAR RNA with high affinities. In the presence of a representative Tat-TAR inhibitor (5 microM TR87), we observed potent and sustained suppression of HIV replication in cultured cells over 24 days. The same concentration of this inhibitor did not exhibit any toxicity in cell cultures or in mice. TR87 was also shown to specifically disrupt Tat-TAR binding in vitro and inhibit Tat-mediated transcriptional activation in vitro and in vivo, providing a strong correlation between its activities and inhibition of HIV-1 replication. These results provide a structural scaffold for further development of new drugs, alone or in combination with other drugs, for treatment of HIV-1-infected individuals. Our results also suggest a general strategy for discovering pharmacophores targeting RNA structures that are essential in progression of other infectious, inflammatory, and genetic diseases.

Animals↗

PubMed2003

New triterpenoids from Corchorus trilocularis.

Two new tetracyclic triterpenoid trilocularol A and trilocularol A 3-glucoside and one pentacyclic triterpenoid tirlocularoside A were isolated from Corchorus trilocularis L., their structure were elucidated as 3beta,6alpha,16alpha,20(S),27-pentahydroxydammar-24(Z)-ene (1), 3beta-D-glucopyranosyloxy-6alpha,16alpha,20(S),27-tetrahydroxydammar-24(Z)-ene (2) and 2alpha,3beta,19alpha,30-tetrahydroxyurs-12-en-24,28-dioic acid 28-O-beta-D-glucopyranosyl ester (3). respectively, on the basis of detailed spectroscopic studies.

Corchorus↗