Biology subjects

Akhter, J.

Publications and source records attributed to Akhter, J..

5 recordsLinked to original sources

bioRxiv2026

Human skin fibrosis with iPSC-derived organoids reveals RUNX2-mediated fibroblast reprogramming

Fibrotic skin diseases are characterized by persistent fibroblast activation and extracellular matrix remodeling, yet the mechanisms governing fibroblast state transitions remain incompletely understood. Here, we established a human iPSC-derived skin organoid model of fibrosis through chronic TGF-{beta} stimulation. Single-cell RNA sequencing combined with immunofluorescence-based spatial analysis revealed dynamic fibroblast state transitions, spatial reorganization, and expansion of activated fibroblast populations during fibrotic remodeling. Integration with human scleroderma single-cell datasets demonstrated conserved fibroblast states and transcriptional programs between organoids and patient tissues. We further identified broad induction of RUNX2 in the dermal compartment during fibrosis, and RUNX2 depletion attenuated fibrotic marker expression. CUT&RUN profiling revealed RUNX2 occupancy at fibrosis-associated loci, including RUNX1 and LOXL2. Using a machine learning-guided screening approach, we identified F0565-0303, a small molecule that suppressed RUNX2-dependent fibrotic programs in vitro and reduced fibrosis in a bleomycin-induced mouse model. Together, these findings establish human skin organoids as a platform for modeling fibrosis and nominate RUNX2 as a potential therapeutic target.

bioengineering↗

bioRxiv2021

Effect of nebulised BromAc(R) on rheology of artificial sputum: relevance to muco-obstructive respiratory diseases including COVID-19

Respiratory diseases such as cystic fibrosis, COPD, bronchiectasis asthma and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Since earlier studies have shown success with BromAc(R) as mucolytic agent for treating a rare disease known as pseudomyxoma peritonei (PMP), we tested the formulation on two gelatinous airway representative sputa models, in order to determine whether similar efficacy exist. The sputum (1.5 ml) lodged in an endotracheal tube was treated to aerosolised N-acetylcysteine, bromelain, or their combination (BromAc(R)) using a nebuliser with 6.0 ml of the agents in phosphate buffer saline, over 25 min. Controls received phosphate buffer saline. The dynamic viscosity was measured before and after treatment using a capillary tube method, whilst the sputum flow (ml/sec) was assessed using a 0.5 ml pipette. Finally, the sequestered agents (concentration) in the sputa after treatment were quantified using standard bromelain and N-acetylcysteine chromogenic assays. Results indicated that bromelain and N-acetylcysteine affected both the dynamic viscosities and pipette flow in the two sputa models, with changes in the former parameter having immense effect on the latter. BromAc(R) showed a greater rheological effect on both the sputa models compared to individual agents. Further, correlation was found between the rheological effects and the concentration of agents in the sputa. Hence, this study indicates that BromAc(R) may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretion, however further studies with patient sputum samples using aerosol BromAc(R) is warranted.

microbiology↗

bioRxiv2021

Bromelain and Acetylcysteine (BromAc) alone and in combination with Gemcitabine inhibits subcutaneous deposits of pancreatic cancer after intraperitoneal injection

ObjectiveGemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier in vitro studies with GEM in combination with Bromelain (Brom) and Acetylcysteine (Ac) indicated a substantial reduction in IC50. Here, we investigated the efficacy and safety of Brom and Ac (BromAc) in the pancreatic cancer model in vivo. DesignBoth low dose and high dose studies for safety and efficacy of BromAc and GEM were conducted in nude mice. Body weight, wellbeing and tumor volume were monitored. At autopsy, tumor weight, tumor density, percentage of tumor necrosis, expression of Ki67 antigen, and immunohistological evaluation of vital organs were compared between the treatment groups. ResultsThe low and high doses of BromAc alone and with chemotherapy agents were safe. A very significant reduction in pancreatic tumor volume, weight, and ki67 were seen with BromAc therapy and was equal to treatment with GEM alone and better than treatment with 5-FU. In addition, tumor density was significantly reduced by BromAc. ConclusionThese encouraging results are the first in vivo evidence of the efficacy of BromAc in pancreatic cancer and provide some mechanistic leads.

cancer biology↗

bioRxiv2020

In vitro study of BromAc on SARS-CoV-2 spike and envelope proteins shows synergy and disintegration at modest concentrations

Background and objectivesSARS-CoV-2 infection is the cause of a worldwide pandemic, currently with limited therapeutic options. Whilst vaccines are at the forefront of the therapeutic initiative, drug repurposing remains a promising approach for SARS-CoV-2 treatment. BromAc (Bromelain & Acetylcysteine) has synergistic action against glycoproteins by the synchronous breakage of glycosidic linkages and disulfide bonds. The spike protein of SARS-CoV-2, formed of glycoprotein and disulfide bridges for stabilization, represents an attractive target as it is essential for binding to the ACE2 receptor in host cells present in nasal mucosa. We sought to determine the effect of BromAc on the Spike and Envelope proteins and its potential to reduce infectivity in host cells. DesignRecombinant Spike and Envelope proteins were treated by single agent and combination BromAc at 50 and 100 {micro}g/20mg/mL and analyzed by electrophoresis. Ultraviolet analysis of disulfide bond reduction was performed for both Spike and Envelope proteins after treatment with Acetylcysteine. In vitro whole virus culture inactivation of pre-treated wild type and an S1/S2 Spike mutant SARS-CoV-2 with BromAc from 25 to 250 {micro}g/20mg/mL was measured by cytopathic effect, cell lysis assay, and replication capacity by RT-PCR. ResultsRecombinant Spike and Envelope SARS-CoV-2 proteins were fragmented by BromAc at both 50 and 100 {micro}g/20mg/mL whilst single agents had minimal effect. Spike and Envelope protein disulfide bonds were reduced by Acetylcysteine. In vitro whole virus culture of both wild type and Spike mutant SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. ConclusionBromAc disintegrates SARS-CoV-2 Spike and Envelope proteins. In vitro tests on whole virus support this finding with inactivation of its replication capacity most strongly at 100 and 250 {micro}g/20mg/mL BromAc, even in Spike mutant virus. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent. Author SummaryThere is currently no suitable therapeutic treatment for early SARS-CoV-2 aimed to prevent disease progression. BromAc is under clinical development by the authors for mucinous cancers due to its ability to alter complex glycoproteins structure. The potential of BromAc on SARS-CoV-2 Spike and Envelope glycoproteins stabilized by disulfide bonds was examined and found to disintegrate recombinant Spike and Envelope proteins whilst reducing disulfide stabilizer bridges. BromAc also showed an inhibitory effect on wild-type and Spike mutant SARS-CoV-2 by inactivation of its replication capacity in vitro. Hence, BromAc may be an effective therapeutic agent for early SARS-CoV-2 infection, despite mutations, and even have potential as a prophylactic in people at high risk of infection.

microbiology↗

bioRxiv2020

Dynamics of the COVID -19 Related Publications

BackgroundThis study aims to analyze the dynamics of the published articles and preprints of Covid-19 related literature from different scientific databases and sharing platforms. MethodsThe PubMed, Elsevier, and Research Gate (RG) databases were under consideration in this study over a specific time. Analyses were carried out on the number of publications as (a) function of time (day), (b) journals and (c) authors. Doubling time of the number of publications was analyzed for PubMed "all articles" and Elsevier published articles. Analyzed databases were (1A) PubMed "all articles" (01/12/2019-12/06/2020) (1B) PubMed Review articles (01/12/2019-2/5/2020) and (1C) PubMed Clinical Trials (01/01/2020-30/06/2020) (2) Elsevier all publications (01/12/2019-25/05/2020) (3) RG (Article, Pre Print, Technical Report) (15/04/2020-30/4/2020). FindingsTotal publications in the observation period for PubMed, Elsevier, and RG were 23000, 5898 and 5393 respectively. The average number of publications/day for PubMed, Elsevier and RG were 70.0 {+/-}128.6, 77.6{+/-}125.3 and 255.6{+/-}205.8 respectively. PubMed shows an avalanche in the number of publication around May 10, number of publications jumped from 6.0{+/-}8.4/day to 282.5{+/-}110.3/day. The average doubling time for PubMed, Elsevier, and RG was 10.3{+/-}4 days, 20.6 days, and 2.3{+/-}2.0 days respectively. In PubMed average articles/journal was 5.2{+/-}10.3 and top 20 authors representing 935 articles are of Chinese descent. The average number of publications per author for PubMed, Elsevier, and RG was 1.2{+/-}1.4, 1.3{+/-}0.9, and 1.1{+/-}0.4 respectively. Subgroup analysis, PubMed review articles mean and median review time for each article were <0|17{+/-}17|77> and 13.9 days respectively; and reducing at a rate of-0.21 days (count)/day. InterpretationAlthough the disease has been known for around 6 months, the number of publications related to the Covid-19 until now is huge and growing very fast with time. It is essential to rationalize the publications scientifically by the researchers, authors, reviewers, and publishing houses. FundingNone

scientific communication and education↗