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1.
Nat Commun ; 15(1): 4720, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830847

RESUMO

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (<2 min fabrication time/patch), and ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we created next-generation patches for instant attachment to tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with extracellular vesicles derived from mesenchymal stem cells demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.


Assuntos
Adesivos Teciduais , Cicatrização , Animais , Humanos , Elasticidade , Células-Tronco Mesenquimais/citologia , Camundongos , Adesivo Tecidual de Fibrina , Masculino , Materiais Biocompatíveis/química
2.
Sci Rep ; 14(1): 9138, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644366

RESUMO

Phosphorene is a unique semiconducting two-dimensional platform for enabling spintronic devices integrated with phosphorene nanoelectronics. Here, we have designed an all phosphorene lattice lateral spin valve device, conceived via patterned magnetic substituted atoms of 3d-block elements at both ends of a phosphorene nanoribbon acting as ferromagnetic electrodes in the spin valve. Through First-principles based calculations, we have extensively studied the spin-dependent transport characteristics of the new spin valve structures. Systematic exploration of the magnetoresistance (MR) of the spin valve for various substitutional atoms and bias voltage resulted in a phase diagram offering a colossal MR for V and Cr-substitutional atoms. Such MR can be directly attributed to their specific electronic structure, which can be further tuned by a gate voltage, for electric field controlled spin valves. The spin-dependent transport characteristics here reveal new features such as negative conductance oscillation and switching of the sign of MR due to change in the majority spin carrier type. Our study creates possibilities for the design of nanometric spin valves, which could enable integration of memory and logic elements for all phosphorene 2D processors.

3.
Mikrochim Acta ; 191(4): 182, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451377

RESUMO

The rapid fabrication is described of binary electrocatalyst based on a highly porous metal-organic framework with zirconium metal core (Zr-MOF) decorated over the graphitic carbon nitride (g-C3N4) nanosheets via facile ultrasonication method. It is used for the robust determination of antipsychotic drug chlorpromazine (CLP) from environmental samples. The electrochemical behaviour of 2D Zr-MOF@g-C3N4 was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies. The crystalline and porous nature of the composite was characterized by XRD and SEM analysis. The functional groups and surface characteristics were investigated by FT-IR, Raman and XPS. The major electrochemical properties of the Zr-MOF@g-C3N4 composite towards CLP detection were analyzed by CV, chronocoulometric (CC), chronoamperometric (CA) and differential pulse voltammetry (DPV) techniques. The composite exhibits a low detection limit (LOD) of 2.45 nM with a linear range of 0.02 to 2.99 µM and attractive sensitivity for CLP. The sensor system shows higher selectivity towards the possible interferences of CLP drug and exhibits better repeatability and stability. Finally, the fabricated sensor system shows a high recovery range varying from 96.2 to 98.9% towards the real samples. The proposed electrochemical probe might be a promising alternative to the prevailing diagnostic tools for the detection of CLP.


Assuntos
Antipsicóticos , Clorpromazina , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia Dielétrica , Eletrodos
4.
Cureus ; 16(1): e52007, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344555

RESUMO

BACKGROUND: The physiological equilibrium of the entire human body's metabolism is significantly influenced by thyroid hormones. Subclinical hypothyroidism, which is often concealed, is connected to iron deficiency anemia and various other hematological disorders. We in the current study tried to determine the prevalence and severity of iron deficiency anemia and investigate the correlation of subclinical hypothyroidism with iron deficiency. METHODS: A total of 100 subjects included in the study were divided into two groups. Group 1 included 50 cases with subclinical hypothyroidism, and Group 2 included 50 healthy age- and sex-matched controls. Hemoglobin (Hb) levels were measured within 24 hours of sample collection using a Sysmex automated cell counter (Kobe, Hyogo, Japan). Thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH)) were measured. RESULTS: Out of 50 cases, 48 (96%) have iron deficiency anemia, and 52 (104%) have subclinical hypothyroidism. Among the cases with iron deficiency anemia, 43 (86%) also have subclinical hypothyroidism. There was a negative correlation between thyrotropin (TSH) and Hb levels. Pearson's correlation coefficient "r" values were -0.86408. The serum ferritin levels of cases were decreased as compared to the healthy controls, and the difference in means for cases and controls in terms of serum ferritin is also statistically significant. CONCLUSION: The prevalence of anemia in subclinical hypothyroidism is significantly elevated, and considering the absence of significant clinical manifestations in the early stages, it is recommended to routinely conduct investigations for early detection, facilitating prompt management. Consequently, our study emphasizes that both overt and subclinical hypothyroidism should be recognized as risk factors for the development of iron deficiency anemia.

5.
Cancer Res Commun ; 4(2): 487-495, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38335300

RESUMO

Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, and forestomach. In addition, CPN mice displayed oral cavity squamous cell carcinoma (OSCC); CP mice bearing wild-type NRF2 expression did not develop oral cavity hyperplasia, dysplasia or OSCC. In both CP and CPN mice, we also observed predominantly abdominal sarcomas and carcinomas. Our data show that in the context of p53 and p16 tumor suppressor loss, NRF2 activation serves oncogenic functions to drive OSCC. CPN mice represent a new model for OSCC that closely reflects the genetics of human HNSCC. SIGNIFICANCE: Human squamous cancers frequently show constitutive NRF2 activation, associated with poorer outcomes and resistance to multiple therapies. Here, we report the first activated NRF2-driven and human-relevant mouse model of squamous cell carcinoma that develops in the background of p16 and p53 loss. The availability of this model will lead to a clearer understanding of how NRF2 contributes to the initiation, progression, and therapeutic response of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/genética , Modelos Animais de Doenças , Neoplasias de Cabeça e Pescoço/genética , Hiperplasia/genética , Neoplasias Bucais/genética , Fator 2 Relacionado a NF-E2/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteína Supressora de Tumor p53/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo
6.
J Family Med Prim Care ; 12(9): 1784-1789, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38024874

RESUMO

Coronavirus disease 2019 (COVID-19) is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both immediate and long-term adverse effects arise out of this disease's aftermath. It involves various organs, which include endocrine glands, nervous system, musculoskeletal system, and other organs. The long-term outcomes of the SARS-CoV-2 infection are influenced by preexisting comorbidities. Genetic, environmental, and immunological factors contribute to the development of various autoimmune diseases, which include Graves' disease (GD). The growing mystery surrounding this virus is exacerbated by auto-inflammatory diseases, such as pediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), which raises concerns about the nature of the virus' connection to the autoimmune and auto-inflammatory sequelae. There is a need to understand the underlying mechanisms of developing GD in post-COVID-19 patients. There are limited data regarding the pathogenesis involved in post-COVID-19 GD. Our goal was to understand the various mechanisms involved in post-COVID-19 GD among patients with confirmed COVID-19 infection. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for 2020, a literature search of medical databases (PubMed, Cochrane Central Register of Controlled Trials, and Scopus) from February 2021 to February 2022 was performed by five authors. The keywords used were "Post COVID-19," "Grave's disease," "Cytokine storm," "Autoimmunity," and "Molecular mimicry." This review revealed three underlying mechanisms that resulted in post-COVID GD, which included cytokine storm, molecular mimicry, ACE2 receptor concentration, and cell-mediated immunity. The full spectrum of the effects of COVID-19 needs to be researched.

7.
Sci Rep ; 13(1): 16599, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789039

RESUMO

Semiconductors with controllable electronic transport coupled with magnetic behaviour, offering programmable spin arrangements present enticing potential for next generation intelligent technologies. Integrating and linking these two properties has been a long standing challenge for material researchers. Recent discoveries in two-dimensional (2D) magnet shows an ability to tune and control the electronic and magnetic phases at ambient temperature. Here, we illustrate controlled spin transport within the magnetic phase of the 2D semiconductor CrOBr and reveal a substantial connection between its magnetic order and charge carriers. First, we systematically analyse the strain-induced electronic behaviour of 2D CrOBr using density functional theory calculations. Our study demonstrates the phase transition from a magnetic semiconductor → half metal → magnetic metal in the material under strain application, creating intriguing spin-resolved conductance with 100% spin polarisation and spin-injection efficiency. Additionally, the spin-polarised current-voltage (I-V) trend displayed conductance variations with high strain-assisted tunability and a peak-to-valley ratio as well as switching efficiency. Our study reveals that CrOBr can exhibit highly anisotropic behaviour with perfect spin filtering, offering new implications for strain engineered magneto-electronic devices.

8.
Biomaterials ; 301: 122260, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37549505

RESUMO

Globally, there are 20 million adolescent girls and young women living with HIV who have limited access to long-acting, effective, women-controlled preventative methods. Additionally, although there are many contraceptive methods available, globally, half of all pregnancies remain unintended. Here we report the first 3D-printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for HIV prevention and contraception. We utilized continuous liquid interface production (CLIP™) to fabricate MPT IVRs in a biocompatible silicone-based resin. Etonogestrel (ENG), ethinyl estradiol (EE), and islatravir (ISL) were loaded into the silicone poly(urethane) IVR in a controlled single step drug loading process driven by absorption. ENG/EE/ISL IVR promoted sustained release of drugs for 150 days in vitro and 14 days in sheep. There were no adverse MPT IVR-related findings of cervicovaginal toxicity or changes in vaginal biopsies or microbiome community profiles evaluated in sheep. Furthermore, ISL IVR in macaques promoted sustained release for 28 days with ISL-triphosphate levels above the established pharmacokinetic benchmark of 50-100 fmol/106 PBMCs. The ISL IVR was found to be safe and well tolerated in the macaques with no observed mucosal cytokine changes or alterations in peripheral CD4 T-cell populations. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls.


Assuntos
Infecções por HIV , Gravidez não Planejada , Gravidez , Humanos , Feminino , Animais , Ovinos , Preparações de Ação Retardada , Administração Intravaginal , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Macaca , Impressão Tridimensional
9.
Int J Disaster Risk Reduct ; 93: 103776, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37303828

RESUMO

Introduction: Individual and community characteristics predictive of knowledge, perception, and attitude on COVID-19, specifically on gender, have not been adequately explored. Objective: To examine the gender differences in COVID-19 knowledge, self-risk perception and public stigma among the general community and to understand other socio-demographic factors which were predictive of them. Method: A nationally representative cross-sectional multi-centric survey was conducted among adult individuals(≥18 yrs) from the community member (N = 1978) from six states and one union territory of India between August 2020 to February 2021. The participants were selected using systematic random sampling. The data were collected telephonically using pilot-tested structured questionnaires and were analyzed using STATA. Gender-segregated multivariable analysis was conducted to identify statistically significant predictors (p < 0.05) of COVID-19-related knowledge, risk perception, and public stigma in the community. Results: Study identified significant differences between males and females in their self-risk perception (22.0% & 18.2% respectively) and stigmatizing attitude (55.3% & 47.1% respectively). Highly educated males and females had higher odds of having COVID-19 knowledge (aOR: 16.83: p < 0.05) than illiterates. Highly educated women had higher odds of having self-risk perception (aOR: 2.6; p < 0.05) but lower public stigma [aOR: 0.57; p < 0.05]. Male rural residents had lower odds of having self-risk perception and knowledge [aOR: 0.55; p < 0.05 & aOR: 0.72; p < 0.05] and female rural residents had higher odds of having public stigma [aOR: 1.36; p < 0.05]. Conclusion: Our study findings suggest the importance of considering thegender differentials and their background, education status and residential status in designing effective interventions to improve knowledge and reduce risk perception and stigma in the community about COVID-19.

10.
Neuropharmacology ; 238: 109643, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37369277

RESUMO

Ghrelin is a peptide that is produced by endocrine cells that are primarily localized in the stomach. Ghrelin receptors (GHSR) are expressed in the brain and periphery. Preclinical and clinical studies support a role for ghrelin in alcohol drinking and seeking. The GHSR has been suggested to be a potential pharmacotherapeutic target for alcohol use disorder (AUD). However, the role of the ghrelin system and its potential modulation by biological sex on binge-like drinking has not been comprehensively investigated. The present study tested six GHSR antagonists in an alcohol binge-like drinking procedure in male and female mice. Systemic administration of the GHSR antagonists JMV2959, PF-5190457, PF-6870961, and HM-04 reduced alcohol intake in both male and female mice. YIL-781 decreased intake in males, and LEAP2 (likely peripherally restricted) did not reduce intake in mice of either sex. We also administered LEAP2 and JMV2959 intracerebroventricularly to investigate whether the effects of GHSR blockade on alcohol intake are mediated by central receptors. The central administration of LEAP2 and JMV2959 decreased alcohol intake, particularly in high-drinking animals. Finally, in a preliminary experiment, an anti-ghrelin vaccine was examined for its potential effect on binge-like drinking and had no effect. In all experiments, there was a lack of meaningful sex differences. These findings suggest that central GHSR mediates binge-like alcohol intake. These data reveal novel pharmacological compounds with translational potential in the treatment of AUD and provide further evidence of the GHSR as a potential treatment target for AUD.


Assuntos
Alcoolismo , Receptores de Grelina , Feminino , Camundongos , Masculino , Animais , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Etanol
11.
J Food Sci Technol ; 60(7): 2001-2011, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37206425

RESUMO

Microfiltration of citrus fruit juices using membrane technology is a promising method for clarification without losing their inherent properties to extend their shelf life. The present work discusses the development of a tubular ceramic microfiltration membrane and its performance in clarifying two kinds of citrus fruit juices, mandarin and sweet orange. The membrane was prepared by the extrusion method from indigenous bentonite clay, exhibited a porosity of 37% with 0.11 µm pore size, and possessed adequate flexural strength of 18 MPa. The fabricated membrane's potential was evaluated by conducting the tangential filtration of both centrifuged and enzyme-treated centrifuged fruit juices. Also, the applied pressure (68.94-344.7 kPa) and crossflow rate (110-150 Lph) were varied to study the clarified juice properties. At low operating conditions, the highest clarity of the juices was identified despite low permeate flux. The desired properties of juices, including pH, citric acid content, and total soluble solids, were unaffected by pretreatment and tangential membrane filtration, whereas the pectin content, which reduces the juice quality, was eliminated entirely. Furthermore, fouling analysis was carried out using Hermia's models, and cake filtration was identified to be dominant for both juices. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05734-y.

12.
Pediatr Rev ; 44(6): 301-310, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37258888

RESUMO

Despite improvements in oral morbidity levels and access to care among the pediatric population, there are still major disparities in the United States. Results of national surveys have documented a decrease in the number of children receiving either a dental examination or a cleaning. This finding is particularly concerning for toddlers and infants, as early preventive dental visits and the establishment of a dental home is cost-effective and leads to enhanced oral health outcomes over the life span. Many infants and toddlers do not visit a dentist, suggesting that the recommendations of the American Academy of Pediatrics and the American Academy of Pediatric Dentistry to establish a dental home are not appropriately adopted.


Assuntos
Cárie Dentária , Lactente , Criança , Humanos , Estados Unidos/epidemiologia , Cárie Dentária/diagnóstico , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Pediatras , Intervenção Educacional Precoce
13.
Toxicol Pathol ; 51(1-2): 77-80, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37083209

RESUMO

Nonclinical toxicity testing (GLP) of prophylactic vaccines to support human clinical trials is outlined in the World Health Organization nonclinical vaccine-development guidelines, which are followed by most regulatory agencies globally. Vaccine GLP toxicity studies include at least two groups: a buffer control (often phosphate-buffered saline) group and a highest anticipated clinical dose formulation group. However, studies may include additional groups, including lower-dose formulation groups and adjuvant-containing formulation control groups. World Health Organization guidelines touch upon expectations for dose group and tissue selection for microscopic evaluation, but there is variation in the interpretation of this aspect of these guidelines between vaccine developers. This opinion piece proposes a scientifically based approach for defining appropriate groups to evaluate in the dosing and recovery phases in nonclinical vaccine toxicity studies, as well as suggestions on selecting tissues for microscopic evaluation at the recovery phase of studies to promote alignment between vaccine manufacturers.


Assuntos
Testes de Toxicidade , Vacinas , Humanos , Testes de Toxicidade/métodos , Vacinas/toxicidade
14.
J Mech Behav Biomed Mater ; 141: 105748, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36898356

RESUMO

The aim of this study was to assess the remineralization efficacy of chicken eggshell-derived nano-hydroxyapatite (CEnHAp) combined with phytosphingosine (PHS) on artificially induced dentinal lesions. PHS was commercially procured whereas CEnHAp was synthesized using microwave-irradiation method and characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), high-resolution scanning electron microscopy-energy-dispersive X-ray spectroscopy (HRSEM-EDX), and transmission electron microscopy (TEM). A total of 75 pre-demineralized coronal dentin specimens were randomly treated with one of the following test agents (n = 15 each): artificial saliva (AS), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), CEnHAp, PHS, and CEnHAp-PHS under pH cycling for 7, 14, and 28 days. Vickers microhardness indenter, HRSEM-EDX, and micro-Raman spectroscopy methods were used to assess the mineral changes in the treated dentin samples. Data were submitted to Kruskal-Wallis and Friedman's two-way analyses of variance (p < 0.05). HRSEM and TEM analysis depicted irregular spherical structure of the prepared CEnHAp with a particle size of 20-50 nm. The EDX analysis confirmed the presence of Ca, P, Na and Mg ions. The XRD pattern showed the characteristic crystalline peaks for hydroxyapatite and calcium carbonate that are present in the prepared CEnHAp. Dentin treated with CEnHAp-PHS revealed highest microhardness values along with complete tubular occlusion compared to other groups at all test time intervals (p < 0.05). Specimens treated with CEnHAp showed increased remineralization than those treated with CPP-ACP followed by PHS and AS groups. The intensity of mineral peaks, as observed in the EDX and micro-Raman spectra, confirmed these findings. Further, the molecular conformation of the collagen's polypeptide chains, and amide-I and CH2 peaks attained peak intensities in dentin treated with CEnHAp-PHS and PHS whereas other groups revealed poor stability of collagen bands. Microhardness, surface topography, and micro-Raman spectroscopy analyses revealed that dentin treated with CEnHAp-PHS have an improved collagen structure and stability as well as highest mineralization and crystallinity.


Assuntos
Casca de Ovo , Análise Espectral Raman , Animais , Espectroscopia de Infravermelho com Transformada de Fourier , Colágeno/análise , Saliva Artificial/química , Durapatita/química , Dentina/química
15.
J Ocul Pharmacol Ther ; 39(3): 215-224, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36880872

RESUMO

Purpose: Bevacizumab-bvzr (Zirabev®), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys. Methods: Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.25 mg/eye/dose once every 2 weeks (3 doses total) for 1 month by bilateral IVT injection, followed by a 4-week recovery phase to evaluate the reversibility of any findings. Local and systemic safety was assessed. Ocular safety assessments included in-life ophthalmic examinations, tonometry (intraocular pressure, IOP), electroretinograms (ERGs), and histopathology. In addition, concentrations of bevacizumab-bvzr were measured in serum and in ocular tissues (vitreous humor, retina, and choroid/retinal pigment epithelium) and ocular concentration-time profiles and serum TKs were evaluated. Results: Bevacizumab-bvzr was tolerated locally and systemically, with an ocular safety profile comparable to the saline or vehicle control group. Bevacizumab-bvzr was observed in both serum and in the evaluated ocular tissues. There were no bevacizumab-bvzr-related microscopic changes or effects on IOP or ERGs. Bevacizumab-bvzr-related trace pigment or cells in vitreous humor (in 4 of 12 animals; commonly associated with IVT injection) and transient, nonadverse, mild ocular inflammation (in 1 of 12 animals) were noted upon ophthalmic examination and fully reversed during the recovery phase. Conclusions: Bevacizumab-bvzr was well tolerated via biweekly IVT administration in healthy monkeys, with an ocular safety profile comparable to saline or its vehicle control.


Assuntos
Medicamentos Biossimilares , Animais , Masculino , Bevacizumab/farmacologia , Macaca fascicularis , Fator A de Crescimento do Endotélio Vascular , Injeções Intravítreas , Toxicocinética , Retina , Inibidores da Angiogênese
16.
Vaccines (Basel) ; 11(2)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36851293

RESUMO

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine candidates encoding immunogens derived from the spike (S) glycoprotein of SARS-CoV-2, encapsulated in lipid nanoparticles (LNPs). Vaccine candidates were administered intramuscularly once weekly for three doses at 30 and/or 100 µg followed by a 3-week recovery period. Clinical pathology findings included higher white blood cell counts and acute phase reactant concentrations, lower platelet and reticulocyte counts, and lower RBC parameters. Microscopically, there was increased cellularity (lymphocytes) in the lymph nodes and spleen, increased hematopoiesis in the bone marrow and spleen, acute inflammation and edema at the injection site, and minimal hepatocellular vacuolation. These findings were generally attributed to the anticipated immune and inflammatory responses to the vaccines, except for hepatocyte vacuolation, which was interpreted to reflect hepatocyte LNP lipid uptake, was similar between candidates and resolved or partially recovered at the end of the recovery phase. These studies demonstrated safety and tolerability in rats, supporting SARS-CoV-2 mRNA-LNP vaccine clinical development.

17.
Biosci Rep ; 43(3)2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36790370

RESUMO

γ-Tubulin ring complex (γ-TuRC), composed of γ-tubulin and multiple γ-tubulin complex proteins (GCPs), serves as the major microtubule nucleating complex in animal cells. However, several γ-TuRC-associated proteins have been shown to control its function. Centrosomal adaptor protein, TACC3, is one such γ-TuRC-interacting factor that is essential for proper mitotic spindle assembly across organisms. ch-TOG is another microtubule assembly promoting protein, which interacts with TACC3 and cooperates in mitotic spindle assembly. However, the mechanism how TACC3-ch-TOG interaction regulates microtubule assembly and the γ-TuRC functions at the centrosomes remain unclear. Here, we show that deletion of the ch-TOG-binding region in TACC3 enhances recruitment of the γ-TuRC proteins to centrosomes and aggravates spindle microtubule assembly in human cells. Loss of TACC3-ch-TOG binding imparts stabilization on TACC3 interaction with the γ-TuRC proteins and it does so by stimulating TACC3 phosphorylation and thereby enhancing phospho-TACC3 recruitment to the centrosomes. We also show that localization of ch-TOG at the centrosomes is substantially reduced and the same on the spindle microtubules is increased in its TACC3-unbound condition. Additional results reveal that ch-TOG depletion stimulates γ-tubulin localization on the spindles without significantly affecting the centrosomal γ-tubulin level. The results indicate that ch-TOG binding to TACC3 controls TACC3 phosphorylation and TACC3-mediated stabilization of the γ-TuRCs at the centrosomes. They also implicate that the spatio-temporal control of TACC3 phosphorylation via ch-TOG-binding ensures mitotic spindle assembly to the optimal level.


Assuntos
Fuso Acromático , Tubulina (Proteína) , Animais , Humanos , Proteínas de Ciclo Celular/metabolismo , Centrossomo/metabolismo , Células HeLa , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/genética , Microtúbulos/metabolismo , Mitose , Fuso Acromático/genética , Fuso Acromático/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
18.
Front Public Health ; 10: 992046, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311615

RESUMO

Objective: To assess factors associated with COVID-19 stigmatizing attitudes in the community and stigma experiences of COVID-19 recovered individuals during first wave of COVID-19 pandemic in India. Methods: A cross-sectional study was conducted in 18 districts located in 7 States in India during September 2020 to January 2021 among adults > 18 years of age selected through systematic random sampling. Data on socio demographic and COVID-19 knowledge were collected from 303 COVID-19 recovered and 1,976 non-COVID-19 infected individuals from community using a survey questionnaire. Stigma was assessed using COVID-19 Stigma Scale and Community COVID-19 Stigma Scale developed for the study. Informed consent was sought from the participants. Univariate and multivariate binary logistic regression analysis were conducted. Results: Half of the participants (51.3%) from the community reported prevalence of severe stigmatizing attitudes toward COVID-19 infected while 38.6% of COVID-19 recovered participants reported experiencing severe stigma. Participants from the community were more likely to report stigmatizing attitudes toward COVID-19 infected if they were residents of high prevalent COVID-19 zone (AOR: 1.5; CI: 1.2-1.9), staying in rural areas (AOR: 1.5; CI:1.1-1.9), belonged to the age group of 18-30 years (AOR: 1.6; CI 1.2-2.0), were male (AOR: 1.6; CI: 1.3-1.9), illiterate (AOR: 2.7; CI: 1.8-4.2), or living in Maharashtra (AOR: 7.4; CI: 4.8-11.3). COVID-19 recovered participants had higher odds of experiencing stigma if they had poor knowledge about COVID-19 transmission (AOR: 2.8; CI: 1.3-6.3), were staying for 6-15 years (AOR: 3.24; CI: 1.1-9.4) in the current place of residence or belonged to Delhi (AOR: 5.3; CI: 1.04-26.7). Conclusion: Findings indicated presence of stigmatizing attitudes in the community as well as experienced stigma among COVID-19 recovered across selected study sites in India during the first wave of COVID-19 pandemic. Study recommends timely dissemination of factual information to populations vulnerable to misinformation and psychosocial interventions for individuals affected by stigma.


Assuntos
COVID-19 , Pandemias , Adulto , Masculino , Humanos , Adolescente , Adulto Jovem , Feminino , Estudos Transversais , COVID-19/epidemiologia , Índia/epidemiologia , Estigma Social
19.
Indian J Med Res ; 155(1): 156-164, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35859441

RESUMO

Background & objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community. Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability. Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement. Interpretation & conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.


Assuntos
COVID-19 , Estigma Social , Humanos , Índia/epidemiologia , Pandemias , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
20.
Antioxidants (Basel) ; 11(7)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35883708

RESUMO

Cigarette smoking has been responsible for causing many life-threatening diseases such as pulmonary and cardiovascular diseases as well as lung cancer. One of the prominent health implications of cigarette smoking is the oxidative damage of cellular constituents, including proteins, lipids, and DNA. The oxidative damage is caused by reactive oxygen species (ROS, oxidants) present in the aqueous extract of cigarette smoke (CS). In recent years, there has been considerable interest in the potential health benefits of dietary polyphenols as natural antioxidant molecules. Epidemiological studies strongly suggest that long-term consumption of diets (fruits, vegetables, tea, and coffee) rich in polyphenols offer protective effects against the development of cancer, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. For instance, green tea has chemopreventive effects against CI-induced lung cancer. Tea might prevent CS-induced oxidative damages in diseases because tea polyphenols, such as catechin, EGCG, etc., have strong antioxidant properties. Moreover, apple polyphenols, including catechin and quercetin, provide protection against CS-induced acute lung injury such as chronic obstructive pulmonary disease (COPD). In CS-induced health problems, the antioxidant action is often accompanied by the anti-inflammatory effect of polyphenols. In this narrative review, the CS-induced oxidative damages and the associated health implications/pathological conditions (or diseases) and the role of diets rich in polyphenols and/or dietary polyphenolic compounds against various serious/chronic conditions of human health have been delineated.

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