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Glucocorticoids induced osteoporosis (GIOP) is a global concern without effective therapies. The present study investigated the potential of the umbilical cord-derived mesenchymal stem cells (UCMSCs) and traditional medicine Piper longum L. in the reversal of GIOP. Twelve-week-old female Swiss Albino mice were subjected to the dexamethasone treatment for 4 weeks to induce GIOP. Further, the mice were randomized into four different groups for treatment, viz., phosphate buffered saline (PBS), UCMSCs, P. longum L. aqueous extract through feed, and a combination of UCMSCs and P. longum L. extract. Post therapy, GIOP mice regained the weight and hair loss in the UCMSCs and P. longum L. extract group. ALP activity and mRNA expression of RunX2, ALP, and OPN were significantly increased. Micro-CT analysis revealed remarkable improvement in key parameters such as bone volume, bone surface density, tissue surface, trabecular thickness, and number. Our results unequivocally demonstrate that a combination of the UCMSCs and P. longum L. is highly effective in the reversal of GIOP as compared to P. longum L. or UCMSCs alone. The therapeutic effect can be attributed to the osteogenic and paracrine potential of UCMSCs and the anti-inflammatory effect of P. longum L., (© 2025 Wiley‐VCH GmbH.)

Background Aims: The clinical translation of mesenchymal stromal cell secretome (MSC-S) has been challenging owing to a lack of appropriate methods in downstream processing. Dialysis is an age-old method of protein purification by the exchange of small molecules through a semi-permeable membrane. In this study, we investigated the potential of three forms of umbilical cord-derived MSC secretome (UC-MSC-S)-native (S), dialyzed (DS), and lyophilized (LDS)-for wound healing applications., Methods and Results: We dialyzed the UC-MSC-S using Slide-A-Lyzer G3 Dialysis Cassettes (20K MWCO) and then lyophilized it to obtain secretome powder. The DS fraction exhibited an 86.01-fold decrease compared with S, whereas LDS showed a 613.71-fold increase in the total protein concentration. Growth factor analysis revealed a significant decrease in the levels of interleukin-6 (IL-6; 54.44-fold), angiopoietin-1 (79.56-fold), angiopoietin-2 (51.76-fold), IL-8 (54.4-fold), platelet endothelial cell adhesion molecule-1 (PECAM-1; 63.25-fold), phosphatidylinositol glycan anchor biosynthesis class F (PIGF; 40.42-fold), vascular endothelial growth factor (VEGF; 39.64-fold), and tumor necrosis factor alpha (TNF-α; 24.62-fold) after dialysis as analyzed by the LEGEND plex multi-analyte flow assay kit on a FACS analyzer. Post-lyophilization, the levels of IL-6 (392.21-fold), angiopoietin-1 (823.04-fold), angiopoietin-2 (397.69-fold), IL-8 (584.83-fold), PECAM-1 (341.28-fold), PIGF (342.85-fold), VEGF (2209.42-fold), and TNF-α (194.4-fold) were enriched in LDS. The highest wound closure (64.07%) and a significant increase in angiogenesis were seen in DLS at the concentration of 1 µg/µL of protein by wound scratch and in ovo yolk sac membrane assay, respectively., Conclusions: Dialysis followed by lyophilization is a simple and cost-effective method to fractionate and enrich the bioactive components of MSC-S without compromising the bioactivity for tailor-made applications., (Copyright © 2025 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Recently, there has been a great interest in the development of innovative wound dressing materials based on natural bioactives, as they can accelerate the healing process and address the issues related to traditional wound dressings. The current study focuses on developing a novel derivative of guar gum (GG) and gallic acid (GA) using a simple, free radical-mediated polymerization reaction aimed at enhancing the antioxidant properties of GG. Multiple spectroscopic investigations were performed to validate the GA-GG conjugate. NMR and FTIR confirmed GA integration, UV spectroscopy indicated changes in electronic transition, DSC analysis suggested a reduction in crystallinity, and XRD revealed structural modifications. SEM revealed a porous structure that reflected its polymerized nature. Due to inadequate mechanical strength and film-forming ability of the synthesized GA-GG conjugate, polyelectrolyte complexation method using chitosan was explored to form a polyelectrolyte complex (PEC) film. The film exhibited a high swelling rate, excellent antioxidant properties, and was both hemocompatible and exhibited improved antimicrobial properties. In vitro , in ovo , and in vivo characterizations were performed to compare the performance of these biocomposite films to those of their counterparts. It promoted angiogenesis in the chick yolk sac membrane and demonstrated good cytocompatibility in cell proliferation studies on the viability of the L929 mouse fibroblast cell line. In vivo wound healing efficacy of the PEC film in wound closure was 94.5% as compared to the untreated disease control group ( p  < 0.001). This work highlights the development of an innovative GA-GG conjugate/chitosan PEC-based film with significant potential for wound healing applications.

In the past 2-3 decades, numerous attempts have been made to create an insulin-secreting β cell line that maintains normal insulin secretion. However, primary β cell cultures have finite life and, therefore, cannot be used for long-term experiments. The most widely used insulin-secreting cell lines are Insulinoma-1, rat insulinoma cell line, hamster pancreatic β cell line, mouse insulinoma, and β tumor cell line. Insulinoma-derived cell lines show infinite growth in tissue culture but exhibit varying differences in their insulin responsiveness to glucose levels compared to normal β cells. Despite difficulties with β cell cultures, these cell lines have offered some useful insights in diabetes research concerning physiological functions and pathological investigations. In this review, we describe insulinoma cell lines used for drug screening, insulin secretion, cell viability, proliferation, and other relevant cellular functions. In addition, we have also incorporated recently developed human β cell lines. These cell lines have provided some helpful insights into physiological activities and pathology in diabetes research, despite challenges with β cell culturing. We propose that these cell lines could also be explored for screening Ayurvedic Rasayanas and homeopathy preparations for their cytotoxicity and insulin secretagogue activities to have evidence-based data on alternative and complementary medicines., (© 2024 John Wiley & Sons Ltd.)

Background: Type 1 diabetes mellitus (T1DM) is a condition marked by elevated blood sugar levels and primarily recognized by the destruction of beta cells caused by an autoimmune attack, which is a significant characteristic of T1DM. Recent studies have demonstrated the regenerative potential of conditioned medium therapy. In light of this, the current research sought to assess the impact of Mesenchymal Stem Cell conditioned media (CM) and CM with resveratrol (CM+ Resveratrol) on the management of T1DM in Swiss albino mice. By leveraging and modifying existing conditioned medium therapy, this study aims to evaluate its effectiveness in treating T1DM., Materials & Methods: Diabetes was induced in animals using the diabetes-inducing agent streptozotocin (STZ). The animals were then divided into five groups: Normal control, Disease Control, Resveratrol, Condition Media, and CM + Resveratrol. Treatments were given to the animals accordingly. The study period was 28 days. During this time, the animals were monitored for foodwater intake twice a week, blood glucose levels, and body weight. At the conclusion of the 28-day study period, biochemical estimations were performed for serum insulin levels, C-peptide levels, anti-inflammatory cytokines levels and pro-inflammatory cytokines levels. Additionally, histopathology of the pancreas was performed., Results: The test groups showed a significant decrease in blood glucose levels, an increase in Cpeptide levels, and a decrease in pro-inflammatory cytokine levels compared to the disease group. However, no statistically significant change within groups was observed in terms of serum insulin and anti-inflammatory cytokine levels. The improvement in diabetic symptoms, such as polyphagia, polydipsia, and weight loss, was observed in the treatment group, along with pancreatic regeneration, which indicated improved insulin secretion., Conclusion: In the current investigation, we concluded that CM and CM+ Resveratrol, as natural immunomodulators, have the capacity to regenerate injured pancreatic beta cells and have antidiabetic action, together with immunomodulating impact. Nonetheless, future studies on this therapy appear to be promising., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Parkinson's disease (PD) is a stressful neurodegenerative disorder affecting millions worldwide. PD leads to debilitating motor and cognitive symptoms such as tremors, rigidity, and difficulty walking. Current therapies for PD are symptomatic and don't address the root cause. Therefore, there is an urgent need for better management and intensive research into alternative therapies. Mesenchymal stem cell (MSC) therapy is among the leading contenders among these promising avenues. We examined preclinical and clinical evidence demonstrating the neuroprotective, anti-inflammatory, and regenerative properties of the MSCs. This review focuses on the complex pathophysiological mechanisms of PD, as well as the perspectives of MSCs and their derivatives, such as secretomes and exosomes, in the clinical management of PD. We also analyzed the challenges and limitations of each approach, including delivery methods, timing of administration, and long-term safety considerations., Competing Interests: Declaration of competing interest The authors declare that they have approved the final version of the manuscript. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article’., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Angiogenesis, the biological mechanism by which new blood vessels are generated from existing ones, plays a vital role in growth and development. Effective preclinical screening is necessary for the development of medications that may enhance or inhibit angiogenesis in the setting of different disorders. Traditional in vitro and, in vivo models of angiogenesis are laborious and time-consuming, necessitating advanced infrastructure for embryo culture., Main Body: A challenge encountered by researchers studying angiogenesis is the lack of appropriate techniques to evaluate the impact of regulators on the angiogenic response. An ideal test should possess reliability, technical simplicity, easy quantifiability, and, most importantly, physiological relevance. The CAM model, leveraging the extraembryonic membrane of the chicken embryo, offers a unique combination of accessibility, low cost, and rapid development, making it an attractive option for angiogenesis assays. This review evaluates the strengths and limitations of the CAM model in the context of its anatomical and physiological properties, and its relevance to human pathophysiological conditions. Its abundant capillary network makes it a common choice for studying angiogenesis. The CAM assay serves as a substitute for animal models and offers a natural setting for developing blood vessels and the many elements involved in the intricate interaction with the host. Despite its advantages, the CAM model's limitations are notable. These include species-specific responses that may not always extrapolate to humans and the ethical considerations of using avian embryos. We discuss methodological adaptations that can mitigate some of these limitations and propose future directions to enhance the translational relevance of this model. This review underscores the CAM model's valuable role in angiogenesis research and aims to guide researchers in optimizing its use for more predictive and robust preclinical studies., Conclusion: The highly vascularized chorioallantoic membrane (CAM) of fertilized chicken eggs is a cost-effective and easily available method for screening angiogenesis, in comparison to other animal models., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Oral squamous cell carcinoma (OSCC) is one of the most prevalent forms of head and neck squamous cell carcinomas (HNSCC) with a poor overall survival rate (about 50%), particularly in cases of metastasis. RNA-based cancer biomarkers are a relatively advanced concept, and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies. This review underlines the function of long non-coding RNAs (lncRNAs) in the OSCC and its subsequent clinical implications. LncRNAs, a class of non-coding RNAs, are larger than 200 nucleotides and resemble mRNA in numerous ways. However, unlike mRNA, lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA, RNA, proteins, or microRNAs depending on concentration and localization in cells. Upregulation of oncogenic lncRNAs and down-regulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers. Targeted inhibition of candidate oncogenic lncRNAs or over-expression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models. The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity. This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival, proliferation, invasion, migration, metastasis, angiogenesis, metabolism, epigenetic modification, tumor immune microenvironment, and drug resistance. Subsequently, we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems, providing details on ongoing research and outlining potential future directions for advancements in this field. In essence, this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2024 The Authors.)

Decellularized tissues are an attractive scaffolds for 3D tissue engineering. Decellularized animal tissues have certain limitations such as the availability of tissue, high costs and ethical concerns related to the use of animal sources. Plant-based tissue decellularized scaffolds could be a better option to overcome the problem. The leaves of different plants offer a unique opportunity for the development of tissue-specific scaffolds, depending on the reticulate or parallel veination. Herein, we decellularized spinach leaves and employed these for the propagation and osteogenic differentiation of dental pulp stem cells (DPSCs). DPSCs were characterized by using mesenchymal stem cell surface markers CD90, CD105 and CD73 and CD34, CD45 and HLA-DR using flow cytometry. Spinach leaves were decellularized using ethanol, NaOH and HCL. Cytotoxicity of spinach leaf scaffolds were analysed by MTT assay. Decellularized spinach leaves supported dental pulp stem cell adhesion, proliferation and osteogenic differentiation. Our data demonstrate that the decellularized spinach cellulose scaffolds can stimulate the growth, proliferation and osteogenic differentiation of DPSCs. In this study, we showed the versatile nature of decellularized plant leaves as a biological scaffold and their potential for bone regeneration in vitro., (© 2024. The Society for In Vitro Biology.)

Background: The therapeutic effectiveness of mesenchymal stem cells (MSCs) and their secretome can be enhanced by means of physical, chemical and biological preconditioning. Arsenicum album 30C (AA30) has been one of the leading homeopathic medicines used in prophylaxis against SARS-CoV-2 infection., Aims: This study aimed to investigate whether AA30 preconditioning could influence the growth factors and cytokine profile of the human dental pulp-derived MSC (DPD-MSC) secretome. Also, to test the efficacy of the AA30-preconditioned DPD-MSC secretome in ameliorating the lipopolysaccharide (LPS)-induced cytokine storm in human peripheral blood mononuclear cells (PBMCs) as an in-vitro cellular model., Methods: The cytotoxicity of AA30 was assessed in DPD-MSCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Growth factors and cytokine levels in the AA30-preconditioned DPD-MSC secretome were analysed by fluorescence-activated cell sorting (FACS) analysis. The angiogenic potential of the AA30-preconditioned DPD-MSC secretome was assessed by chick yolk-sac membrane (YSM) assay. Culture medium with 0.001% ethanol was used as vehicle control. The efficacy of the AA30-preconditioned DPD-MSC secretome in ameliorating the cytokine storm was assessed in LPS pre-treated PBMCs. The mRNA and protein expression of inflammatory markers such as IL-1β, IL-6 and IL-10 were analysed by using RT-PCR and FACS analysis respectively., Results: AA30 did not exhibit cytotoxicity in the concentration range of 1% to 50%. Furthermore, the AA30-preconditioned DPD-MSC secretome exhibited a significant increase in the levels of angiogenic factors, such as human angiopoietin-2, EPO and PDGF-AA, and decreased levels of cytokines, such as TNF-α, CXCL-8 and IL-6. The AA30-preconditioned DPD-MSC secretome showed augmented angiogenesis compared to vehicle controls. The DPD-MSC secretome ameliorated LPS-induced mRNA and protein expression of IL-1β, IL-6 and IL-10 in PBMCs., Conclusion: The AA30-preconditioned DPD-MSC secretome augmented angiogenesis and ameliorated the LPS-induced cytokine storm in human PBMCs in vitro . Our data demonstrate that AA30 preconditioning enhances the therapeutic potency of MSCs and their secretome., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Recent evidence suggests the immense potential of human mesenchymal stem cell (hMSC) secretome conditioned medium-mediated augmentation of angiogenesis. However, angiogenesis potential varies from source and origin. The hMSCs derived from the oral cavity share an exceptional quality due to their origin from a hypoxic environment. Our systematic review aimed to compare the mesenchymal stem cells (MSCs) derived from various oral cavity sources and cell-derived secretomes, and evaluate their angiogenic potential. A literature search was conducted using PubMed and Scopus from January 2000 to September 2020. Source-wise outcomes were systematically analyzed using in vitro , in vivo , and in ovo studies, emphasizing endothelial cell migration, tube formation, and blood vessel formation. Ninety-four studies were included in the systematic review, out of which 4 studies were subsequently included in the meta-analysis. Prominent growth factors and other bioactive components implicated in improving angiogenesis were included in the respective studies. The findings suggest that oral tissues are a rich source of hMSCs. The meta-analysis revealed a positive correlation between dental pulp-derived MSCs (DPMSCs) and stem cells derived from apical papilla (SCAP) compared to human umbilical cord-derived endothelial cell lines as a control. It shows a statistically significant positive correlation between the co-culture of human umbilical vein endothelial cells (HUVECs) and DPMSCs with tubule length formation and total branching points. Our meta-analysis revealed that oral-derived MSCs (dental pulp stem cells and SCAP) carry a better angiogenic potential in vitro than endothelial cell lines alone. The reviewed literature illustrates that oral cavity-derived MSCs (OC-MSCs) increased angiogenesis. The present literature reveals a dearth of investigations involving sources other than dental pulp. Even though OC-MSCs have revealed more significant potential than other MSCs, more comprehensive, target-oriented interinstitutional prospective studies are warranted to determine whether oral cavity-derived stem cells are the most excellent sources of significant angiogenic potential., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Stem cells obtained from the body tissue, such as adipose tissue, dental pulp and gingival tissue. Fresh tissue is often used to isolate and culture for regenerative medicine. However, availability of tissue as and when required is one of the measure issue in regenerative medicine. Cryopreservation of tissue provides benefit over tissue availability, storage for significant amount of period and helps preserve the original cell structures. The effects of cryopreservation of gingival tissue for mesenchymal stem cell (MSC) are not well documented; however this process is of increasing importance for regenerative therapies. This study examined the effect of cryopreservation on the long term survival the whole gingival biopsy tissue. We studied cell outgrowth, cell morphology, MSC surface-markers and differentiation of mesenchymal stem cells derived from cryopreserved gingiva. In this study, gingival tissue was cryopreserved for 3, 6, 9 months. Cryopreserved tissue has been thawed and cells were isolated by using explant culture method. The fresh and cryopreserved gingival tissue cells were cultured and characterized for surface marker analysis, CFU-f, population doubling time, and osteogenic, chondrogenic and adipogenic differentiation. The fresh and cryopreserved tissue has similar stem cell properties. Results indicate that cryopreservation of the entire gingival tissue does not affect the properties of stem cells. This opens door for gingival tissue banking for future use in periodontology and regenerative medicine., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals exhibit increased adipogenesis and decreased osteogenesis. We investigated the potential of adipose tissue-derived MSCs (ADMSCs) secretome obtained from healthy individuals in restoring the tumor necrosis factor-α (TNF-α) mediated imbalance in the adipo/osteogenic differentiation in the dental pulp-derived MSCs obtained from T2DM individuals (dDPMSCs)., Methods: dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of (a) induction cocktail, (b) induction cocktail + TNF-α, and (c) induction cocktail+ TNF-α + ADMSCs-secretome (50%) for 15 and 21 days resp. Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software. Molecular expression of the key genes involved was analyzed by using reverse-transcription polymerase chain reaction (RT-PCR)., Results: Treatment of TNF-α augmented the adipogenesis (9571 ± 765 vs. 19,815 ± 1585 pixel, p  < 0.01) and decreased the osteogenesis (15,603 ± 1248 vs. 11,894 ± 951 pixel, p  < 0.05) of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively. Interestingly, dDPMSCs differentiated along with TNF-α and 50% ADMSCs secretome exhibited enhanced osteogenesis (11,894 ± 951 vs. 41,808 ± 3344 pixel, p  < 0.01) and decreased adipogenesis (19,815 ± 1585 vs. 4480 ± 358 pixel, p  < 0.01). Additionally, dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg ( p  < 0.01), C/EBPa ( p  < 0.05), and FAS ( p  < 0.01) whereas mRNA expression of Runx2 ( p  < 0.05), Osterix ( p  < 0.01), and OCN ( p  < 0.05) was upregulated as revealed by the RT-PCR analysis., Conclusion: ADMSCs secretome from healthy individuals restore the TNF-α influenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future., Competing Interests: All authors declare no conflict of interest., (© 2024 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Background: In traditional medicine, Xanthium strumarium is used as an anti-inflammatory and anti-arthritic plant-based medicine. Human Dental Pulp Stem Cells (hDPSCs) are an ideal in vitro model for drug and bioactive compound screening. This study assessed the potential of X. strumarium aqueous extract on hDPSCs differentiation towards the osteogenic lineage., Materials and Methods: HDPSCs were isolated and cultured by explant method and characterized by surface marker expression, Colony Forming units fibroblasts (CFU-F), Population Doubling time (PDT), and tri-lineage differentiation. X. strumarium aqueous seed extract (XSE) was prepared and its cytotoxic effect on hDPSCs was examined by MTT assay. The effect of XSE on hDPSC differentiation into osteocytes was investigated by biochemical staining and gene expression., Results: The hDPSCs were positive for CD73, CD90, and CD105 and negative for CD34, CD45, and HLA-DR surface markers. The cells had a colony-forming ability with a PDT of 44.91 h. The hDPSCs differentiated into osteocytes, chondrocytes, and adipocytes. The XSE concentration of 15 μg/ml had a significant increase in hDPSC viability. Alizarin Red S staining revealed that XSE treatment enhanced calcium accumulation and matrix mineralization in hDPSCs. XSE treatment also increased osteonectin and IL-6 transcript expression in osteogenesis-induced hDPSCs., Conclusion: X. strumarium aqueous extract is a suitable candidate for bone repair because it promotes osteogenic differentiation in hDPSCs. Therefore this could be explored further in the treatment of bone disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The mesenchymal Stem Cells (MSCs) is one of the leading contender in therapeutic management of cytokine storm implicated in the COVID-19 and other inflammatory conditions. This study was aimed to investigate the effect of Interferon gamma (IFN-γ) and Ascorbic Acid (AA) preconditioning on the secretome of the human Umbilical Cord Derived MSCs (UCMSCs) and their potential to ameliorate the lipopolysaccharide (LPS) induced cytokine storm in the human peripheral blood mononuclear cells (PBMCs). UCMSCs were preconditioned with IFN-γ, AA and secretome (UCMSCs-S, IFNγ-UCMSCs-S and AA-UCSMCs-S) was analysed for the levels of growth factors and cytokines by flow cytometry. The potential of secretome to ameliorate cytokine storm and augment angiogenesis was assessed in the LPS induced PBMCs and yolk sac membrane (YSM) assay respectively. The mRNA transcript and protein levels of IL-6, IL-1β and TNF-α was analysed by RT-PCR and flow cytometry respectively. IFNγ-UCMSCs-S and AA-UCSMCs-S ameliorated the LPS induced cytokine storm as revealed by the decreased mRNA and protein expression of IL-6, IL-1β and TNF-α as compared to the UCMSCs-S. IFNγ-UCMSCs-S and AA-UCSMCs-S augmented angiogenesis in YSM assay. Furthermore, IFNγ and AA preconditioning of UCMSCs exhibited distinct growth factors and cytokine profile in the secretome. Our results unequivocally show that IFNγ and AA preconditioning of MSCs could give better therapeutic outcomes in the cell mediated therapies for COVID-19 and other inflammatory conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Diabetes occurs due to insulin deficiency or less insulin. To manage this condition, insulin administration as well as increased insulin sensitivity is required, but exogeneous insulin cannot replace the sensitive and gentle regulation of blood glucose levels same as β cells of healthy individuals. By considering the ability of regeneration and differentiation of stem cells, the current study planned to evaluate the effect of metformin preconditioned buccal fat pad (BFP) derived mesenchymal stem cells (MSCs) on streptozotocin (STZ) induced diabetes mellitus in Wistar rats., Materials & Methods: The disease condition was established by using a diabetes-inducing agent STZ in Wistar rats. Then, the animals were grouped into disease control, blank, and test groups. Only the test group received the metformin-preconditioned cells. The total study period for this experiment was 33 days. During this period, the animals were monitored for blood glucose level, body weight, and food-water intake twice a week. At the end of 33 days, the biochemical estimations for serum insulin level and pancreatic insulin level were performed. Also, histopathology of the pancreas, liver and skeletal muscle was performed., Results: The test groups showed a decline in the blood glucose level and an increase in the serum pancreatic insulin level as compared to the disease group. No significant change in food and water intake was observed within the three groups, while body weight was significantly reduced in the test group when compared with the blank group, but the life span was increased when compared with the disease group., Conclusion: In the present study, we concluded that metformin preconditioned buccal fat pad-derived mesenchymal stem cells have the ability to regenerate damaged pancreatic β cells and have antidiabetic activity, and this therapy is a better choice for future research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Type 1 diabetes mellitus is a complex disease defined by the loss of pancreatic cells, which leads to complete insulin insufficiency. The Diabetes Control and Problems Trial defines the aims of Type 1 diabetes therapy as achieving adequate glycaemic control, and preventing and avoiding recurrent bouts of hypoglycaemia. Despite ongoing efforts to improve insulin therapy regimens, the actual hormone substitute therapy treats just the symptoms of the disease, with no influence on disease pathology or etiopathogenesis. In recent decades, there has been a lot of interest in preventative techniques in high-risk patients, based on the theory that if a therapeutic intervention is adopted early in the disease, it can help maintain endogenous cell function by protecting the remaining cell reservoir from autoimmune attack., Methods: Based on preclinical and clinical data, we have discussed some immunotherapeutic in this meta-analysis. We referred to the preclinical and clinical studies for teplizumab and rituximab from authentic databases and compiled the data. We used statistical analysis to do a meta-analysis., Results: In two immunotherapeutic anti-CD3 antibodies and anti-CD20 antibodies examples, teplizumab and rituximab, respectively, shows better efficacy as well as fewer side effects. We have discussed this drug briefly based on their mechanism of action and meta-analysis, which compare clinical efficacy., Conclusion: Immunotherapeutic can be a better option for preventing and protecting type one diabetes. Since, the existing literature does not have enough data to support any single drug concluding the same will not be appropriate. Hence further studies are required wherein different drugs can be compared with similar sample sizes for each group of drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The human gingiva-derived mesenchymal stem cells (hGMSCs) possess a great potential to develop the cell-based therapy for diabetes due to its unscarred healing capacity and reparative potential. In this current study, we isolated, cultured and characterised the GMSCs and explored their potential to differentiate into Insulin Producing Cell Clusters (IPCCs)., Methods: The cells derived from gingival tissues exhibited fibroblast-like morphology. The flow cytometric analysis revealed positive expression of CD73(97.43%), CD90(95.05%), and CD105(93.17%) and negative expression of CD34(0.05%), CD45(0.09%), and HLA-DR (0.025) surface markers. We then converted this adherent fibroblast-like GMSCs into floating IPCCs using a sequential three-step protocol containing a different combination of differentiating agents. Initially, the presence of insulin in IPCCs was confirmed by dithizone staining. Glucose-stimulated insulin secretion (GSIS) assay confirmed that IPCCs secrete insulin in response to glucose., Results: Generated IPCCs express pancreatic markers such as insulin, pdx1, glucagon, GLUT4 and GLUT2 as evidenced by RT-PCR analysis. Our results unequivocally showed that IPCCs can be generated from gingiva which is a potential source of postnatal MSCs. Our results offer the IPCCs generated from hGMSCs a platform for screening anti-diabetic drugs and a new autologous source of tissue for islet transplantation for the treatment of diabetes., Conclusions: Our results unequivocally demonstrate for the first time that hGMSCs can be used as an attractive non-invasive tissue source for generating IPCCs, which can be employed in diabetes research for screening antidiabetic agents and also for transplantation in type 1 diabetic patients as autologous source without the need of immunosuppression., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Epidemiological data have proved the association of consumption of areca nut with the causation of oral submucous fibrosis (OSF). OSF is a chronic inflammatory disease with the potential for malignant transformation from 7 to 13%. The establishment of animal models makes it easier for researchers to focus on the therapeutic options to combat this disease further. We developed and compared two areca nut extract (ANE) administration methods in Swiss albino mice to establish OSF. This study compared an invasive intrabuccal injection technique with a non-invasive intraoral droplet administration. The duration of induction was around 12 weeks. Histopathology (H&E, Masson's trichrome staining) and gene expression analysis (COL-I, COL-II, and α-SMA) were performed using RT-PCR to confirm the OSF in animals. Our study showed that ANE administration through the intraoral droplet method exhibited significantly higher fibrosis than the intrabuccal injections, as evidenced by the H&E and Masson's trichrome staining. Furthermore, intraoral administration of ANE significantly upregulated the mRNA expression of COL-I, COL-II, and α-SMA, as revealed by the RT-PCR analysis. The non-invasive droplet method could simulate the absorption of areca nut seen in humans through daily dosing. This study establishes the intraoral droplet method as an efficient and non-invasive method to administer the ANE to develop OSF. These findings will aid in the efficient development of OSF animal models for interventional studies, including screening novel drugs in the reversal of the OSF., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The human oral cavity harbours complex microbial communities with various commensal microorganisms that play pivotal roles in maintaining host health and immunity but can elicit local and systemic diseases. The role of commensal microorganisms in SARS-CoV-2 infection and disease susceptibility and enrichment of opportunistic pathobionts in the oral cavity is poorly understood. The present study aims to understand the altered landscape of the oral microbiome and mycobiome in SARS-CoV-2 infected patients (n = 30) and its correlation with risk factors compared to non-infected individuals (n = 24) using targeted amplicon sequencing. Diminution of species richness, an elevated abundance of opportunistic pathogens (Veillonella, Acinetobacter, Klebsiella, Prevotella, Gemella, and Streptococcus) and impaired metabolic pathways were observed in the COVID-19 patients. Similarly, altered oral mycobiome with enrichment of known respiratory disease causing pathogenic fungi were observed in the infected individuals. The data further suggested that reduction in immunomodulatory microorganisms lowers the protection of individuals from SARS-CoV-2. Linear discriminant analysis identified several differentially abundant taxa associated with risk factors (ageing and co-morbidities). We also observed distinct bacterial and fungal community structures of elderly infected patients compared to the younger age group members making them highly vulnerable to SARS-CoV-2 infection and disease severity. Furthermore, we also assessed the dynamics of the oral microbiome and mycobiome in symptomatic and asymptomatic patients, host types, co-morbidities, and viral load in the augmentation of specific pathobionts. Overall, the present study demonstrates the microbiome and mycobiome profiling of the COVID-19 infected individuals, the data further suggests that the SARS-CoV-2 infection triggers the prevalence of specific pathobiont., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Abnormal angiogenesis hamper blood vessel proliferation implicated in various biological processes. The current method available to clinically treat patients to enhance angiogenesis is administering the angiogenic growth factors. However, due to a lack of spatiotemporal control over the substantial release of these factors, numerous drawbacks are faced such as leaky vasculature. Hence, stem-cell-based therapeutic applications are running their race to evolve as potential targets for deranged angiogenesis. In clinical dentistry, adequate tissue vascularization is essential for successful endodontic therapies such as apexogenesis and apexification. Furthermore, wound healing of the extraction socket and tissue regeneration post-surgical phase of treatment including implant placement require angiogenesis as a foundation for the ultimate success of treatment. Mesenchymal stem cells (MSCs) secrete certain growth factors and cytokines in the culture medium during the proliferation. These factors and cytokines are responsible for various biological activities inside human body. Oral cavity-derived stem cells can secrete growth factors that enhance angiogenesis., Aim: The aim of the study was to investigate the angiogenic potential of conditioned medium (CM) of MSCs derived from different oral sources., Methods: Oral tissues such as dental pulp of adult and deciduous teeth, gingiva, and buccal fat were used to isolate dental pulp MSCs (DPSCs), exfoliated deciduous teeth, gingival MSCs, and buccal fat derived MSCs. MSCs conditioned medium (CM) from passage four cells from all the sources were obtained at 48 h interval and growth factor analysis was performed using flow cytometry. To assess the functionality of the CM, Chick Yolk Sac Membrane (YSM) assay was performed., Results: CM obtained from DPSCs showed higher levels of vascular endothelial growth factor, fibroblast growth factor, and hepatocyte growth factor as evidenced by flow cytometry. Furthermore, DPSC-CM exhibited significantly higher pro-angiogenic potential when assessed in in-ovo YSM assay., Conclusion: DPSCs so far seems to be the best source as compare to the rest of oral sources in promoting angiogenesis. A novel source of CM derived from buccal fat stem cells was used to assess angiogenic potential. Thus, the present study shows that CM derived from oral cavity-derived-MSCs has a dynamic and influential role in angiogenesis., Relevance for Patients: CM derived from various oral sources of MSCs could be used along with existing therapies in medical practice where patients have compromised blood supply like in diabetes and in patients with debilitating disorders. In clinical dentistry, adequate tissue vascularization is essential for successful wound healing, grafting procedures, and endodontic therapies. DPSCs-CM shows better angiogenic potential in comparison with other oral sources of MSCs-CM. Our findings could be a turning point in the management of all surgical and regenerative procedures requiring increased angiogenesis., Competing Interests: All authors declare no conflict of interest., (Copyright: © 2022 Author(s).)

Chronic Obstructive Pulmonary Disease (COPD) is a disorder characterized by narrow alveoli as a result of emphysema. As such, there is no treatment to cure this disorder completely, and existing drugs only delay the progression of the disease. In recent years, the stem cell secretome as a drug is remarkably used as a regenerative therapy. In particular, cell-free therapy approaches offer great opportunities for the treatment of COPD. However, a few issues, such as the delivery of stem cell secretome as a drug to the alveolar region, have obstructed their application in clinical scales. To address these challenges, a combination of stem-cells secretome as a drug with nanotechnology could be a smart solution. We suggest that the combinational approach of delivering nanoparticles loaded with stem cell secretome could be a translational medicine approach for the successful outcome of COPD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The translation of Traditional Medicines (TMs) such as Ayurveda, and Traditional Chinese Medicine into clinical practice remains obstructed due to lack of scientific evidence by means of safety, quality, standardization, clinical efficacy, and mode of action. These limitations can be attributed to the lack of synonymous invitro models which reflect invivo features. Human mesenchymal stem cells (hMSCs) have emerged as an efficient cell source for regenerative medicine and tissue engineering. In this review, the authors discuss how hMSCs can be used as an invitro platform to screen herbs described in TMs using modern methods such as evaluation of its potential, safety, quality, mode of action, etc. Integration of traditional knowledge systems like Ayurveda and hMSCs as a platform to screen and study TMs using modern tools will effectively increase the validity of TMs as evidence-based medicine., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The Indian Traditional Medicine, Ayurveda prescribes Piper longum L. popularly known as Long Pepper (Pippali) for the treatment of inflammatory and degenerative diseases. Therapeutic benefits of Piper longum L. are mainly attributed to the anti-inflammatory and arthritic potential., Aim of the Study: This study was aimed to explore the activity of Piper longum L. fruit extract on proliferation and osteogenic differentiation of human Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) to find out it's possible role as anti-osteoporotic agent., Materials and Methods: Proliferation of WJMSCs treated with Piper longum L. fruit extract was assessed by MTT assay and Cell Cycle Analysis. Effect of Piper longum L. preconditioning on osteogenic differentiation was performed. Ca 2+ accumulation and matrix mineralization (Von Kossa and Alizarin Red Staining), alkaline phosphatase (ALP) activity and gene expression of key mRNA (RT PCR) was analyzed., Results: Significant increase in the proliferation of WJMSCs was observed upon treatment of Piper longum L. at 5 μg/mL (P < 0.001) which can be attributed to the significant decrease in apoptotic cells (P < 0.05) as evidenced by cell cycle analysis. Preconditioning of Piper longum L. (10-100 μg/mL) enhanced Ca 2+ accumulation and matrix mineralization as observed by Von Kossa and Alizarin Red staining where ALP activity was elevated 3.6 folds as compared to untreated WJMSCs (P < 0.001). RT-PCR analysis exhibited up regulation of Runx2, Osterix, ALP and OPN mRNAs., Conclusions: We demonstrate for the first time that Piper longum L. fruit extract enhanced osteogenic differentiation of WJMSCs. This finding can be clinically translated into development of an anti-osteoporotic agent., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The scarcity of human cadaver islets for transplantation in patients with Diabetes Mellitus (DM) has necessitated the search for alternative islet sources. With advancing islet biology research, Islet-Like Clusters (ILCs) derived from stem cells have demonstrated potential for treating DM and in novel drug discovery programs for drug and cytotoxicity testing. In vitro differentiation of ILCs from stem cells also provides an opportunity to mimic the in vivo islet developmental pathways. In vitro derived ILCs are often considered immature as they do not respond to glucose challenges efficiently. However, the in vitro and in vivo performance of ILCs can be improved by pharmacological preconditioning. In this review, we discuss how ILCs generated from human postnatal tissues can be utilized as an in-vitro model to study cytotoxicity, drug screening and enhancement of transplantation efficacy. The use of human cadaver islets is not permitted for research purposes in India. Under these restrictions, the application of ILCs in drug screening and their role in complementing, reducing, and replacing animal testing will evolve as a reliable platform for in vitro screening as well as for stem cell-based treatment in DM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Management of Type 2 Diabetes (T2DM) with existing strategies of life style and pharmaceutical interventions has gained limited success as evidenced by its uncontrolled progression. Two key organs which are involved in pathophysiology of T2DM are liver and pancreas, both are the derivatives of endoderm with common precursor. In the invertebrates, hepatopancreas performs function of both liver and pancreas. It is known that derangement in glycolysis, neoglucogenesis, and glycogenolysis lead to hyperglycemia in T2DM although insulin levels are high. Several studies have reported implication of abnormal liver function in the development of metabolic syndrome i.e. T2DM. Partial hepatectomy has been shown to improve glycemic status in animal models of diabetes. This could be because liver and pancreas share same regenerating factors. These evidences suggest that abnormal liver status can impair pancreatic beta cell function and survival along with peripheral insulin resistance. We therefore hypothesize that restoring deranged liver functions may aid in the better control and management of T2DM. If found true, it may shift current intervention strategy towards liver rather than pancreas in the treatment of T2DM., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Oral submucous fibrosis is the direct consequence of a sustained pro-inflammatory environment characterized by excessive collagen deposition causing tissue fibrosis, and progressive degeneration of vital structures including muscle. The pathogenesis of oral submucous fibrosis is largely mediated by the pro-inflammatory, pro-fibrotic cytokines, excessive oxidative stress, abnormal angiogenesis, and epithelial to mesenchymal transition. Mesenchymal stem cells largely known for their regenerative potential have shown to have an immunomodulatory, anti-fibrotic, anti-oxidative, and angiogenic potential. Thus, mesenchymal stem cells, when introduced in an oral submucous fibrosis micro-environment, could potentially counter the progressive fibrosis. The present hypotheses discuss the various pathogenic aspects of oral submucous fibrosis and the properties of mesenchymal stem cells which could aid in halting the disease progression., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pharmacological factors used to induce insulin resistance (IR) in in vitro models may not mimic the full in vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabetic serum (DS) to induce IR and investigate whether adipose-derived mesenchymal stem cell conditioned medium (ADMSC-CM) reverses DS-induced IR., Methods: DS was obtained from newly diagnosed T2DM patients. IR was induced in differentiated 3T3-L1 cells by employing dexamethasone, tumor necrosis factor alpha (TNF-α), palmitate and DS. Glucose uptake (2-[N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino]-2-deoxyglucose(2-NBDG) uptake assay), intracellular levels of reactive oxygen species (ROS), and superoxide radicals (O 2- ) (fluorescence microscopy and fluorometry) were analyzed in control and experimental samples. mRNA expression of key genes involved in glucose transport and inflammation were analyzed by using reverse transcription polymerase chain reaction (RT-PCR). Pro-inflammatory cytokines and phospho-insulin receptor substrate (IRS) (Ser-307) protein expression were analyzed by fluorescence activated cell sorter analysis. Statistical significance was determined by using one-way ANOVA followed by Tukey's multiple comparison tests., Results: ADMSC-CM significantly increased the DS-mediated decrease in 2-NBDG uptake (11.01 ± 0.50 vs . 7.20 ± 0.30, P  < 0.01) and reduced DS-driven ROS (fluorescence count, 6.35 ± 0.46 vs . 9.80 ± 0.10, P  < 0.01) and O 2- (fluorescence count, 3.00 ± 0.10 vs . 4.60 ± 0.09, P  < 0.01) production. Further, the ADMSC-CM restored DS-induced down regulation GLUT4 (1.52-fold, P  < 0.05) as well as the up-regulation of PPARγ (0.35-fold, P  < 0.01), and IKKβ (0.37-fold, P  < 0.01) mRNA, and phospho-IRS (Ser-307) protein expression compared to the baseline (median fluorescence intensity, 88,192 ± 2720 vs . 65,450 ± 3111, P  < 0.01). DS induced IR, similar to the traditionally used pharmacological factors, namely dexamethasone, TNF-α, and palmitate, which can be attributed to the significantly higher pro-inflammatory cytokines levels (TNF-α (2.28 ± 0.03 pg/mL vs . 2.38 ± 0.03 pg/mL, P  < 0.01), interleukin 6 (IL)-6 (1.94 ± 0.02 pg/mL vs . 2.17 ± 0.04 pg/mL, P  < 0.01), IL-17 (2.16 ± 0.02 pg/mL vs . 2.22 ± 0.002 pg/mL, P  < 0.05), and interferon gamma (IFN-γ) (2.07 ± 0.02 pg/mL vs . 2.15 ± 0.04 pg/mL, P  < 0.05)) in DS., Conclusions: DS can be explored as a novel inducer of IR in in vitro studies with further standardization, substituting the conventionally used pharmacological factors. Our findings also affirm the validity of ADMSC-CM as a prospective insulin sensitizer for T2DM therapy., Competing Interests: None., (© 2020 Chinese Medical Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Insulin resistance (IR) is a constituent part of Type 2 Diabetes Mellitus (T2DM). Conditioned medium from Adipose derived Mesenchymal Stem Cells (ADMSCs-CM) has been shown to reverse IR. However, its effect on cellular stress is not well established. The objective of this study was to explore the effect of ADMSCs-CM on reactive oxygen species, mitochondrial membrane potential (ΔΨm), endoplasmic reticulum (ER) stress and expression of oxidative and inflammatory stress induced serine kinases (SISK) which are pathophysiologically linked to IR. In insulin resistant, 3T3-L1 adipocytes and C2C12 myoblast cell culture models, glucose uptake was assayed by 2-NBDG uptake. Immunomodulatory cytokines, intracellular reactive oxygen species generation, ΔΨm and protein expression of JNK1, IKKβ and phospho-IRS1 (307) were analyzed using FACS. mRNA expression of ER stress markers (CHOP1 and IRE1) and SISK (JNK1, IKKβ, ERK1 and S6K1) were analyzed using RT-PCR. ADMSCs-CM effectively improve glucose uptake as evidenced by 2-NBDG uptake assay. FACS analysis showed that ADMSCs-CM possessed significantly higher levels of IL-6 and IL-10. ADMSCs-CM decreased intracellular generation of reactive oxygen species where it restored ΔΨm in C2C12 cells. ADMSCs-CM mediated reduction in ER stress was confirmed by down-regulation in CHOP1 and IRE1 mRNA expression. ADMSCs-CM treatment showed significant down-regulation of SISK mRNA expression including IKKβ, JNK, ERK and S6K1. Our results unequivocally demonstrate for the first time the mechanism of action of ADMSCs-CM in amelioration IR by reducing oxidative and inflammatory cellular stress. This study identifies SISK as potential therapeutic targets for T2DM therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Mesenchymal Stem Cells (MSCs) are multipotent stem cells which are being explored for various clinical applications. Isolation and in-vitro expansion of MSCs remain important in achieving desired cell number for the therapy. However, in-vitro proliferation of MSCs is often associated with senescence and early onset of apoptosis which limits its therapeutic ability and long term clinical use. Tinospora cordifolia and Withania somnifera are used widely in Ayurveda: the traditional Indian system of medicine and are reported to have rejuvenating and anti-aging potential. In the present study, we investigated the effect of Tinospora cordifolia and Withania somnifera on proliferation and senescence of wharton's jelly MSCs (WJMSCs) in-vitro., Methods: WJMSCs were treated in culture medium with Tinospora cordifolia leaf and Withania somnifera root extracts to examine their effect on proliferation and senescence properties of WJMSCs. Proliferation of WJMSCs was assayed by cell count, MTT, BrdU incorporation assay, cell cycle analysis and Ki67 mRNA expression. Senescence was demonstrated using β-galactosidase senescence assay and associated mRNA markers., Results: Culture medium supplemented with Tinospora cordifolia leaf and Withania somnifera root extracts exhibited significant increase in proliferation of WJMSCs as evidenced by cell count and MTT assay. Cell cycle analysis using propidium iodide showed increase in G2/M phase and decrease in apoptotic cells. BrdU incorporation and upregulation of proliferation marker ki67 by RT PCR showed increased DNA synthesis/proliferation in Tinospora cordifolia and Withania somnifera extract treated MSCs. Delayed senescence was confirmed by β-galactosidase senescence assay and down regulation of senescence marker p21., Conclusion: Our results demonstrate for the first time that Tinospora cordifolia and Withania somnifera extracts support proliferation and inhibit senescence in WJMSCs making them suitable candidates as supplements for in-vitro expansion without affecting the cell viability indicating its non-toxic nature., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Nanosized (8-9 nm) Nd doped and Ag coated TiO(2) nanoparticles have been synthesized by sol-gel method. The physicochemical properties of these particles were investigated by X-ray diffraction (XRD), diffuse reflectance UV-visible (DRUV) spectra and Brunauer-Emmett-Teller (BET) surface area analysis. The antibacterial activities of the samples were studied for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) both, under the light and dark conditions. The results reveal that the extent of activity shows the order as undoped TiO(2)