Corrigendum to: Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano.

In this correction, the Editor in Chief suggested revising the publication of Figures 3 and 8E in the article after the correction in numeric value. Below is the corrected version of the figures [1]. The electronic version of the article can be found in "Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano" in the journal Current Gene Therapy, 2018, 18(5), 307-323. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The original article can be found online at: https://www.eurekaselect.com/article/93056.

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.

Toxicological evaluation of banana and milk combination as incompatible diet - An experimental exploration of Samyoga viruddha concept.

BACKGROUND: Food is the basic requirement and an essential part of all living beings which sustains life. A lot of emphasize has been given to food in the classics of Ayurveda and a detailed description of food which are both wholesome and unwholesome have been described. Viruddhahara (incompatible food) is a unique concept explained in Ayurveda which, in long run, may be harmful to the body. OBJECTIVE(S): Intake of Kadaliphala (Musa paradisiaca. Linn, a variety of banana) and cow milk is an example of Samyoga Viruddha (incompatibility with reference to combination of things). This combination is routinely consumed by people. The present study was planned to evaluate the toxicological implication of their combination on wistar rats. MATERIALS AND METHODS: A subacute toxicity study was conducted on Wistar rats following the repeated dose 28-day oral toxicity study in rodents, 407 - OECD guidelines. Different haematological and biochemical parameters along with histopathology of important organs were carried out to assess the toxicological implication of the combination. RESULTS: Repeated administration of the combination of Kadaliphala (Banana) and cow milk showed statistically significant increase in SGOT & urea and statistically significant decrease in creatinine. Significant decrease was observed in the food intake, faecal wet weight and faecal water in the 7th day of study, food conversion ratio in the 14th day of study, in the food intake, faecal wet weight and faecal water in the 21st day of study and significant decrease in the food conversion ratio in the 28th day of study. In histopathological examination, the test drug administered group showed mild to moderate myocarditis in the sections from heart. In sections from liver of two rats of test group, diffused micro fatty changes were observed. In sections from spleen; mild to moderate increase in the white pulp portion was observed. CONCLUSION: Marked variation in SGOT, urea and creatinine levels and alteration in sections of heart, liver and spleen are indicative of mild toxicological implications of the combination of banana and milk. Continuous intake of this incompatible combination may hence prove harmful to the body.

Remarkable migration propensity of dental pulp stem cells towards neurodegenerative milieu: An in vitro analysis.

Stem cell therapy provides a ray of hope for treating neurodegenerative diseases (ND). Bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in neuroregeneration. However, drawbacks like painful bone marrow extraction, less proliferation and poor CNS engraftment following systemic injections of BM-MSC prompt us to search for alternate/appropriate source of MSC for treating ND. In this context, dental pulp stem cells (DPSC) could be an alternative to BM-MSC as it possess both mesenchymal and neural characteristic features due to its origin from ectoderm, ease of isolation, higher proliferation index and better neuroprotection. A study on the migration potential of DPSC compared to BM-MSC in a neurodegenerative condition is warranted. Given the neural crest origin, we hypothesize that DPSC possess better migration towards neurodegenerative milieu as compared to BM-MSC. In this prospect, we investigated the migration potential of DPSC in an in vitro neurodegenerative condition. Towards this, transwell, Matrigel and chorioallantoic membrane (CAM) migration assays were carried-out by seeding hippocampal neurons in the lower chamber and treated with 300 µM kainic acid (KA) for 6 h to induce neurodegeneration. Subsequently, the upper chamber of transwell was loaded with DPSC/BM-MSC and their migration potential was assessed following 24 h of incubation. Our results revealed that the migration potential of DPSC/BM-MSC was comparable in non-degenerative condition. However, following injury the migration potential of DPSC towards the degenerating site was significantly higher as compared to BM-MSC. Furthermore, upon exposure of naïve DPSC/BM-MSCs to culture medium derived from neurodegenerative milieu resulted in significant upregulation of homing factors like SDF-1alpha, CXCR-4, VCAM-1, VLA-4, CD44, MMP-2 suggesting that the superior migration potential of DPSC might be due to prompt expression of homing factors in DPSC compared to BM-MSCs.

Role of salvage therapy in chemo resistant or recurrent high-risk gestational trophoblastic neoplasm.

OBJECTIVES: To assess the importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia (HR GTN) after failure of first line multiagent chemotherapy. METHODS: This retrospective study involving women with HR GTN treated at Kidwai cancer institute from 2000 to 2015. Initial chemotherapy consisted of etoposide, methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Thirty one patients who had incomplete response or relapsed were treated with various drug combinations employing etoposide and platinum agents. Adjuvant surgery and radiation were used in selected patients. Clinical response, survival and factors affecting outcomes were analysed. RESULTS: Thirty one (37.8%) of the 82 patients developed resistance or relapsed after EMA-CO.Of these 25 (80.6%) had lasting complete response to salvage therapy. Salvage chemotherapy included, EMA EP alone in-15, EMA EP followed with BIP in-1, EMAEP followed with VAC in-2, EMA EP followed by TC and VAC in-1, EMA EP followed by TC in-6, TC followed by IA in-1 patient. Irradiation was given to 6 patients for brain metastasis, 1 for spine metastasis, 1 for pelvic tumor, and 1 for mediastinal mass. Operative procedures were hysterectomy in 9, conservative uterine tumour resection in 4 and excision of resistant lung lesion in one. Median follow up 25 (80.6%) patients was 2 years. Complete response to salvage therapy was seen in 25 (80.6%) patients. Overall survival after salvage therapy was 87.1% with median follow up of 2 years. Remission and survival was significantly influenced by ßhCG level at the start of salvage therapy (p<0.001 and 0.006) but not with the stage or with WHO score. CONCLUSIONS: Salvage therapy with platinum/etoposide based drug regimens in conjunction with surgery and radiation, was successful in achieving significant cure and survival in HR-GTN patients.

Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano.

INTRODUCTION: Mesenchymal Stem Cell (MSC) therapy in recent years has gained significant attention. Though the functional outcomes following MSC therapy for neurodegenerative diseases are convincing, various mechanisms for the functional recovery are being debated. Nevertheless, recent studies convincingly demonstrated that recovery following MSC therapy could be reiterated with MSC secretome per se thereby shifting the dogma from cell therapy to cell "based" therapy. In addition to various functional proteins, stem cell secretome also includes extracellular membrane vesicles like exosomes. Exosomes which are of "Nano" size have attracted significant interest as they can pass through the bloodbrain barrier far easily than macro size cells or growth factors. Exosomes act as a cargo between cells to bring about significant alterations in target cells. As the importance of exosomes is getting unveil, it is imperial to carry out a comprehensive study to evaluate the neuroprotective potential of exosomes as compared to conventional co-culture or total condition medium treatments. OBJECTIVE: Thus, the present study is designed to compare the neuroprotective potential of MSC derived exosomes with MSC-condition medium or neuron-MSC-co-culture system against kainic acid induced excitotoxicity in in vitro condition. The study also aims at comparing the neuroprotective efficacy of exosomes/condition medium/co-culture of two MSC viz., neural crest derived human Dental Pulp Stem Cells (hDPSC) and human Bone-Marrow Mesenchymal Stem Cells (hBM-MSC) to identify the appropriate MSC source for treating neurodegenerative diseases. RESULT: Our results demonstrated that neuroprotective efficacy of MSC-exosomes is as efficient as MSC-condition medium or neuron-MSC co-culture system and treating degenerating hippocampal neurons with all three MSC based approaches could up-regulate host's endogenous growth factor expressions and prevent apoptosis by activating cell survival PI3K-B-cell lymphoma-2 (Bcl-2) pathway. CONCLUSION: Thus, the current study highlights the possibilities of treating neurodegenerative diseases with "Nano" size exosomes as opposed to transplanting billions of stem cells which inherit several disadvantages.

Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis.

BACKGROUND: Neurodegenerative diseases comprise a group of disorders for which no treatment is available till date. Stem cell based therapy offers great hope and promise. However, stem cell transplantation is associated with certain disadvantages like poor targeted migration, engraftment and survival of the transplanted cells. MATERIAL & METHOD: Exosomes, a type of extracellular membrane vesicle released by all cell types including stem cells, offer an alternative to stem cell transplantation. Exosome carry a wide array of biomolecules and are implicated in exhibiting substantial benefits in the repair/regeneration of the injured tissue. Thus, exosomes offer an alternative therapeutic approach as a substitute of cell transplantation. In order to utilize exosomes for therapeutic purpose, it is essential to evaluate the appropriate passage number and the dosage to avoid possible cytotoxic effects. Here, we isolated exosomes from different passages of rat bone marrow mesenchymal stem cells (BM-MSC) and analysed the neuroprotective potential of BM-MSC exosomes in an in vitro model of excitotoxicity. RESULT: Our results demonstrated that the exosomes isolated from early passage of rat BM-MSC exhibited more efficient neuroprotective potential as opposed to later passages derived exosomes. Furthermore, the neuroprotective efficacy of exosome is dosage dependent. i.e. the lower dosage of exosomes was found to be neuroprotective, whereas higher dosage of exosomes (from later passages) was found to be detrimental to neurons. The early passage derived exosomes protected neurons through anti-apoptotic, anti-necrotic and anti-oxidant mechanisms. CONCLUSION: Our study suggests that adult stem cells derived exosomes could be a potential therapeutic agent to confer neuroprotection in neurodegenerative diseases like Alzheimer's disease.

A clinical study on the efficacy of Panchavalkala cream in Vrana Shodhana w.s.r to its action on microbial load and wound infection.

BACKGROUND: The science of wound healing is advancing rapidly, particularly as a result of new therapeutic approaches. The wound healing effect of different herbal ointments have been enormous and are in wide practice these days. AIM: To evaluate the efficacy of Panchavalkala cream over wound debridement (wound infection and microbial load). MATERIALS AND METHODS: Ghanasatwa (water extract) of the individual drugs of Panchavalkala was prepared and the extract formulated as herbal ointment. This was used to treat patients of infected chronic non healing wounds. The signs and symptoms of infection were graded before and during the course of treatment. Tissue biopsy to estimate the microbial load prior to and during the course of treatment was done. RESULTS: The clinical symptoms like Slough, swelling, redness, pain, discharge, tenderness, and malodor in wounds showed statistically significant reduction following treatment. The microbial load of the wounds was also reduced significantly. CONCLUSION: In most of the cases, there was a progressive reduction in the microbial load with time, during the course of treatment indicating the efficacy of the formulation in reducing the microbial load and thus controlling infection, facilitating wound healing.