Noreen Latief

Stem cells are extensively used for regenerative purposes as they are unspecialized cells capable of renewal and differentiation. Growth factors like vascular endothelial growth factor (VEGF) play a crucial role in enhancing the regenerative potential of stem cells. The present study was designed to elucidate the effects of VEGF preconditioning in accelerating the regenerative potential of adipose-derived stem cells (ADSCs) for wound healing. In vivo study was carried out using female Sprague Dawley (SD) rats randomly divided into three groups, i.e., VEGF preconditioned ADSCs transplanted group (Pre-Tx), normal ADSCs transplanted group (N-Tx) and control group. ADCS were isolated from female SD rats and treated with VEGF for the Pre-Tx group. At 21st day post-transplantation, the wound in the Pre-Tx group was completely closed. However, the wound was not fully healed in the N-Tx group and the Control group. For further analysis, the experimental area of skin tissues was taken from all groups and examined histologically. The cellularity and granulation were thicker in the pre-Tx group and thicker in the pre-Tx group and thicker, indicating rapid wound recovery. Furthermore, the polymerase chain reaction results also confirmed the down-regulation of apoptotic marker caspase3, which indicates less cell death at the injury site and up-regulation of certain growth factors like IGF, sdf1α and some other markers like E cadherin and vimentin. RT-PCR analysis revealed significant up-regulation of all these factors in the pre-Tx group compared to other groups. These results suggest that VEGF pre-conditioning improves the reparative potency of ADSCs by increasing their survival rate and stimulating the secretion of various growth factors having crucial involvement in angiogenesis and recovery of damaged tissue.

One major aspects to consider while dealing with osteoarthritis is oxidative stress. This deleterious oxidative stress is responsible for the increased production of Reactive Oxygen Species and triggers several inflammatory pathways, including Mitochondrial Inflammation Pathway (MIP), which leads the cell to apoptosis. Chondrocytes, under oxidative stress, are unable to synthesize cartilage efficiently. S-Allyl-L-Cysteine (SAC) is known to be a potent natural, water-soluble antioxidant derived from garlic whose antioxidant properties have been evaluated in several diseases at the molecular level; other than osteoarthritis. Herein, we investigated the potential of S-Allyl-L-Cysteine (SAC) preconditioning of chondrocytes against oxidative stress-mediated mitochondrial inflammation. SAC priming alleviated oxidative stress-induced injuries by significantly improved cell viability, morphology and activated cell migration. In addition, decreased lactate dehydrogenease, increased superoxide dismutase release and retention of glycosaminoglycans were observed.SAC preconditioning ameliorated the injurious effects of oxidative stress as revealed by significant downregulation in gene expression of hypoxia-induciblefactor 1α (Hif-1α), Xanthine Oxidase (XO), Caspase-9 (Casp-9), Caspase-3(Casp-3), Interleukin 1 beta (IL-1β) and inducible nitric oxide synthase (iNOS). These findings suggest that SAC preconditioning might enhance the antioxidant and anti-inflammatory efficacy of chondrocytes by regulating the MIP pathway and improving cellular responses.

Background: Bone is a mineralized dynamic tissue, helps to protect and support the body. Osteoarthritis damages the cartilage and is responsible for the degeneration of the bone. Many cell-based therapies are available to repair the damage however, the non-availability of autologous cells and slows healing during regeneration of the damaged bone present major constraints. Hence, there is a need to search for a convenient and easily available cell source that can not only be used to repair the bone but can also enhance its regenerative potential. β-glycerophosphate, dexamethasone, and L-ascorbic-2-phosphate can differentiate mesenchymal stem cells (MSCs) into osteocytes. So far, the interaction of these compounds with osteocytes-specific proteins has not been studied. In this study, in silico analysis was performed to investigate the interaction of proteins with osteocytes specific compounds at the amino acids level.Methods: 3D structures of Dexamethasone and L-ascorbic-2-phosphate (ascorbic acid) were drawn using Molecular Operating Environment (MOE). Then absorption, distribution, metabolism, and excretion (ADME) analysis was achieved using an online tool of “Swiss Package”. By Ramachandran plot, the predicted model of ALPL, MMP13, Osteonectin, and RunX2 proteins were evaluated. Then docking of these proteins with Dexamethasone and L-ascorbic-2-phosphate was performed.Results: L-ascorbic-2-phosphate and Dexamethasone docked within the binding pockets of ALPL, RunX2, MMP13, and Osteonectin proteins, expressed in the bone cells. These compounds also showed good drug-likeness and pharmacokinetics properties.Conclusion: It is concluded that β-glycerophosphate, dexamethasone, and L-ascorbic-2-phosphate are novel substrates for osteogenic differentiation. These compounds could increase the healing and regenerative potential of bone cells by enhancing the expression of osteocytes specific proteins.Keywords: Bone; Osteoarthritis; β-glycerophosphate; Dexamethasone; L-ascorbic-2-phosphate; Docking; Differentiation; Mesenchymal stem cells (MSCs); Osteonectin Editorial Expression of Concern08 July 2025: Following publication of this paper, the internal audit (consequent to concerns on quality raised by Web of Science) notified Advancements in Life Sciences about problems in use of English language. By this Editorial Expression of Concern, we alert the scientific community as we address the errors.Editorial Note25 July 2025: You are viewing the latest version of this article having minor corrections related to the use of English language. Expression of concern is hereby revoked.

Inflammatory microenvironment after transplantation affects the proliferation and causes senescence of adipose-derived mesenchymal stem cells (hADMSCs) thus compromising their clinical efficacy. Priming stem cells with herbal extracts is considered very promising to improve their viability in the inflammatory milieu.Aesculus indica(A.indica) is used to treat many inflammatory diseases in Asia for decades. Herein, we explored the protective role ofA.indicaextract on human adipose-derived Mesenchymal Stem Cells (hADMSCs) against Monosodium Iodoacetate (MIA) induced stressin vitro.A.indicaameliorated the injury as depicted by significantly enhanced proliferation, viability, improved cell migration and superoxide dismutase activity. Furthermore, reduced lactate dehydrogenase activity, reactive oxygen species release, senescent and apoptotic cells were detected inA.indicaprimed hADMSCs. Downregulation of NF-κB pathway and associated inflammatory genes, NF-κB p65/RelA and p50/NF-κB 1, Interleukin 6 (IL-6), Interleukin 1 (IL-1β), Tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 13 (MMP-13) were observed inA.indicaprimed hADMSCs as compared to stressed hADMSCs. Complementary to gene expression,A.indicapriming reduced the release of transcription factor p65, inhibitory-κB kinase (IKK) α and β, IL-1β and TNF-α proteins expression. Our data elucidates thatA.indicaextract preconditioning rescued hADMSCs against oxidative stress and improved their therapeutic potential by relieving inflammation through regulation of NF-κB pathway.

Pullulanase type I (PulA) is a debranching enzyme that specifically cleaves α-1,6-glycosidic linkages in pullulan. Pullulan has not only diverse applications in food industry but also has immune-stimulatory effects on B and T cells, and found to enhance the production of various anti-inflammatory cytokines in human. Moreover, pullulan has been suggested as a possible anti-cancer drug delivery agent without adjuvant due to its unique structure. The process of pullulan degradation is unresolved due to imprecise pullulanase structural characteristics. Therefore, the present study aimed to understand the structural and functional characteristics of pullulanase enzyme from Geobacillus thermopakistaniensis MAS1 strain using various computational approaches. The physio-chemical topographies and secondary structure of GT_PulA were explored using ProPram, InterPro and SMART. Various tools like I-TASSER, ModRefiner, RAMPAGE, PROCHECK and MOE 2009.10 were used to construct and verify the 3D structural model. The structural elucidation confirmed the significant domains, i.e., CBM48, CBM2, and TIM barrel having catalytically active residues, and conserved region YNGWDP. CBM2 domain along with TIM barrel has a capacity to bind different ligands and proved favorable for multiple substrate catalyses. These structural properties can have a potential effect on enhancing enzymatic activity of GT_PulA enzyme.

Mesenchymal stem cells (MSCs) are being used to treat many diseases as they exhibit great regenerative potential. However, MSC’s transplantation sometimes does not yield the maximum regenerative outcome as they are unable to survive in inflammatory conditions. Several approaches including preconditioning are used to improve the survival rate of mesenchymal stem cells. One such recently reported approach is preconditioning MSCs with plant extracts. The present study was designed to evaluate the effect of Daphne mucronata extract on stressed human adipose-derived mesenchymal stem cells (hADMSCs). Isolated hADMSCs were preconditioned with different concentrations of Daphne muconata extract and the protective, proliferative, antioxidant and anti-inflammatory effect was assessed through various assays and expression analysis of inflammatory markers regulated through NF-κB pathway. Results suggest that preconditioning hADMSCs with Daphne mucronata increased the cell viability, proliferative and protective potential of hADMSCs with a concomitant reduction in LDH, ROS and elevation in SOD activity. Moreover, both the ELISA and gene expression analysis demonstrated down regulations of inflammatory markers (IL1-β, TNF-α, p65, p50, MMP13) in Daphne mucronata preconditioned hADMSCs as compared to stress. This is the first study to report the use of MIA induced oxidative stress against hADMSC’s and effect of Daphne mucronata on stressed hADMSCs. Results of these studies provided evidence that Daphne mucronata protects the hADMSCs during stress conditions by down regulating the inflammatory markers and hence increase the viability and proliferative potential of hADMSCs that is crucial for transplantation purposes. Graphical abstract