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1.
Artigo em Inglês | MEDLINE | ID: mdl-38748642

RESUMO

A coating that can be activated by moisture found in respiratory droplets could be a convenient and effective way to control the spread of airborne pathogens and reduce fomite transmission. Here, the ability of a novel 6-hydroxycatechol-containing polymer to function as a self-disinfecting coating on the surface of polypropylene (PP) fabric was explored. Catechol is the main adhesive molecule found in mussel adhesive proteins. Molecular oxygen found in an aqueous solution can oxidize catechol and generate a known disinfectant, hydrogen peroxide (H2O2), as a byproduct. However, given the limited amount of moisture found in respiratory droplets, there is a need to enhance the rate of catechol autoxidation to generate antipathogenic levels of H2O2. 6-Hydroxycatechol contains an electron donating hydroxyl group on the 6-position of the benzene ring, which makes catechol more susceptible to autoxidation. 6-Hydroxycatechol-coated PP generated over 3000 µM of H2O2 within 1 h when hydrated with a small amount of aqueous solution (100 µL of PBS). The generated H2O2 was three orders of magnitude higher when compared to the amount generated by unmodified catechol. 6-Hydroxycatechol-containing coating demonstrated a more effective antimicrobial effect against both Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria when compared to unmodified catechol. Similarly, the self-disinfecting coating reduced the infectivity of both bovine viral diarrhea virus and human coronavirus 229E by as much as a 2.5 log reduction value (a 99.7% reduction in viral load). Coatings containing unmodified catechol did not generate sufficient H2O2 to demonstrate significant virucidal effects. 6-Hydroxycatechol-containing coating can potentially function as a self-disinfecting coating that can be activated by the moisture present in respiratory droplets to generate H2O2 for disinfecting a broad range of pathogens.

2.
Surg Clin North Am ; 104(3): 503-515, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677816

RESUMO

Pilonidal disease and hidradenitis suppurativa affect healthy young adults, causing discomfort and pain that leads to loss of work productivity and should be approached in a personalized manner. Patients with pilonidal disease should engage in hair removal to the sacrococcygeal region and surgical options considered. Hidradenitis suppurativa can be a morbid and challenging disease process. Medical management with topical agents, antibiotics, and biologics should be used initially but wide local excision should be considered in severe or refractory cases of the disease.


Assuntos
Hidradenite Supurativa , Seio Pilonidal , Humanos , Hidradenite Supurativa/terapia , Hidradenite Supurativa/cirurgia , Hidradenite Supurativa/complicações , Hidradenite Supurativa/diagnóstico , Seio Pilonidal/cirurgia , Seio Pilonidal/terapia , Seio Pilonidal/diagnóstico , Remoção de Cabelo/métodos
3.
J Surg Case Rep ; 2024(1): rjad735, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38250132

RESUMO

Recurrent hyperparathyroidism (HPT) after initial parathyroid surgery occurs rarely in an ectopic location. The rare phenomenon of parathyromatosis may be the cause of this. We present the case of a 59-year-old woman with recurrent HPT, which presented as a new ectopic mediastinal parathyroid gland 13 years after initial 3.5 gland parathyroidectomy. A 1.5 × 1.3 cm lesion was discovered as an incidental finding in the pretracheal region, closely abutting the aortic arch. An aspirate revealed oncocytic cells, which were positive for parathyroid hormone, confirming a mediastinal parathyroid nodule. Sestamibi scan confirmed an avid nodule in the mediastinum. This patient had multiple co-morbidities but was asymptomatic of HPT. It was therefore decided at multi-disciplinary team discussion that she should undergo surveillance. To our knowledge, no such presentations have been reported in the literature. Thus, our case report is a unique addition of an atypical presentation of HPT.

4.
Cureus ; 15(9): e44608, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37795054

RESUMO

INTRODUCTION: Assessing bone condition holds significant value in the diagnosis, treatment planning, and prognosing the periodontal disease; its importance is undeniable. The main aim of the present study was to evaluate the accuracy of alveolar bone measurements due to periodontal disease using cone-beam computed tomography (CBCT), by comparing with surgical measurements, considered as the gold standard. MATERIALS AND METHODS: A prospective cross-sectional study included a sample of 40 individuals diagnosed with chronic periodontitis who required periodontal surgery. A total of 202 sites were assessed for vertical and horizontal bone loss in the anterior (76 sites) and posterior (126 sites) teeth. Bone loss was measured using CBCT and a UNC 15 periodontal probe during the surgical intervention, and then compared. The statistical analysis involved employing a Student's t-test to compare measurements. Unpaired t-tests and correlation analyses were conducted using Pearson's correlation coefficient test. To establish statistical significance, a threshold of p<0.05 was considered appropriate. RESULTS: The statistical analysis carried out on the mean values of CBCT and direct surgical measurements for vertical bone loss demonstrated a significant difference (p<0.01). However, the values obtained for horizontal bone loss did not display statistical significance. A strong correlation of 0.94-0.99 existed between surgical and CBCT measurements. A statistically significant distinction was observed between the two methods in measuring bone loss at the distal and palatal sites of the anterior teeth. CONCLUSION: Both CBCT and direct surgical measurement exhibit comparable accuracy potential in assessing alveolar bone loss. CBCT provides an accessibility advantage by enhancing visual access to challenging sites during surgical interventions, including palatal and distal areas of the teeth.

5.
Natl J Maxillofac Surg ; 14(2): 321-325, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661986

RESUMO

Skeletal Class III malocclusion possess a difficult challenge to treat for clinicians. They are multifactorial and include genetic and environmental factors. Early intervention of Class III needs orthopedic correction, whereas, in adults, orthodontic camouflage can be done to treat mild cases while severe skeletal discrepancies demand orthognathic surgery along with orthodontic therapy. In this case report, a case of mandibular prognathism with Bilateral Sagittal Split Osteotomy (BSSO) setback was presented.

6.
Cell Mol Life Sci ; 80(10): 309, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770649

RESUMO

Bacterial endophthalmitis is a severe complication of eye surgeries that can lead to vision loss. Current treatment involves intravitreal antibiotic injections that control bacterial growth but not inflammation. To identify newer therapeutic targets to promote inflammation resolution in endophthalmitis, we recently employed an untargeted metabolomics approach. This led to the discovery that the levels of S-nitroso-L-glutathione (GSNO) were significantly reduced in an experimental murine Staphylococcus aureus (SA) endophthalmitis model. In this study, we tested the hypothesis whether GSNO supplementation via different routes (oral, intravitreal) provides protection during bacterial endophthalmitis. Our results show that prophylactic administration of GSNO via intravitreal injections ameliorated SA endophthalmitis. Therapeutically, oral administration of GSNO was found to be most effective in reducing intraocular inflammation and bacterial burden. Moreover, oral GSNO treatment synergized with intravitreal antibiotic injections in reducing the severity of endophthalmitis. Furthermore, in vitro experiments using cultured human retinal Muller glia and retinal pigment epithelial (RPE) cells showed that GSNO treatment reduced SA-induced inflammatory mediators and cell death. Notably, both in-vivo and ex-vivo data showed that GSNO strengthened the outer blood-retinal barrier during endophthalmitis. Collectively, our study demonstrates GSNO as a potential therapeutic agent for the treatment of intraocular infections due to its dual anti-inflammatory and cytoprotective properties.


Assuntos
Endoftalmite , Infecções Oculares Bacterianas , Infecções Estafilocócicas , Camundongos , Humanos , Animais , Modelos Animais de Doenças , Endoftalmite/tratamento farmacológico , Endoftalmite/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Inflamação/tratamento farmacológico , Staphylococcus aureus , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Glutationa , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Administração Oral
7.
Int J Pharm ; 642: 123110, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37302672

RESUMO

Developing biofunctionalized ceramic bone substitutes with phytobioactives for their sustained delivery is highly desired to enhance the osteo-active potential of ceramic bone substitutes, reduce the systemic toxicity of synthetic drugs, and increase the bioavailability of phytobioactives. The present work highlights the local delivery of phytobioactives of Cissus quadrangularis (CQ) through nano-hydroxyapatite (nHAP) based ceramic nano-cement. The phytoconstituent profiling represented the optimized CQ fraction to be rich in osteogenic polyphenols and flavonoids like quercetin, resveratrol, and their glucosides. Further, CQ phytobioactives-based formulation was biocompatible, increased bone formation, calcium deposition, proliferation, and migration of cells with simultaneous alleviation of cellular oxidative stress. In the in vivo critical-sized bone defect model, enhanced formation of highly mineralized tissue (BV mm3) in CQ phytobioactives functionalized nano-cement (10.5 ± 2 mm3) were observed compared to the control group (6.5 ± 1.2 mm3). Moreover, the addition of CQ phytobioactives to the bone nano-cement increased the fractional bone volume (BV/TV%) to 21 ± 4.2% compared to 13.1 ± 2.5% in non-functionalized nano-cement. The results demonstrated nHAP-based nano-cement as a carrier for phytobioactives which could be a promising approach for neo-bone formation in different bone defect conditions.


Assuntos
Substitutos Ósseos , Cissus , Osteogênese , Durapatita , Cerâmica
8.
Front Artif Intell ; 6: 1124182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181733

RESUMO

We present a methodology for using machine learning for planning treatments. As a case study, we apply the proposed methodology to Breast Cancer. Most of the application of Machine Learning to breast cancer has been on diagnosis and early detection. By contrast, our paper focuses on applying Machine Learning to suggest treatment plans for patients with different disease severity. While the need for surgery and even its type is often obvious to a patient, the need for chemotherapy and radiation therapy is not as obvious to the patient. With this in mind, the following treatment plans were considered in this study: chemotherapy, radiation, chemotherapy with radiation, and none of these options (only surgery). We use real data from more than 10,000 patients over 6 years that includes detailed cancer information, treatment plans, and survival statistics. Using this data set, we construct Machine Learning classifiers to suggest treatment plans. Our emphasis in this effort is not only on suggesting the treatment plan but on explaining and defending a particular treatment choice to the patient.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36749176

RESUMO

Developing advanced methods for effective bone reconstructive strategies in case of critical bone defects caused by tumor resection, trauma, and other implant-related complications remains a challenging problem in orthopedics. In the clinical management of bone diseases, there is a paradigm shift in using local drugs at the injury site; however, the dead space created during the surgical debridement of necrotic bone and soft tissues (periosteum and underlying muscle) leads to ineffective bone formation, thereby leading to secondary complications, and thus calls for better regenerative approaches. In this study, we have utilized an exosome-functionalized doxorubicin-loaded biodegradable nanocement (NC)-based carrier along with a Cissus quadrangularis (CQ) extract-laden antioxidant herbal membrane for simultaneously managing the periosteum as well as bone formation in the tumor resection model of osteosarcoma. We initially evaluated the efficacy of scaffolds for in vitro mineralization and bone formation. To examine the in vivo effectiveness, we developed a human osteosarcoma cell line (Saos-2)-induced tumor xenograft model with a critical-sized bone defect. The findings revealed that doxorubicin released from NC was successful in killing the tumor cells and was present even after 30 days of implantation. Additionally, the incorporation of exosomes aided the bone formation, resulting in around a 2.6-fold increase in the bone volume compared to the empty group as evaluated by micro-CT. The herbal membrane assisted in the development of periosteum and mineralizing bone callous as validated through histological and immunofluorescence analysis. Thus, our findings describe a one-step biomaterial-based cell-free approach to regenerate bone in osteosarcoma and prevent further fracture due to the complete development of periosteum and lost bone.

10.
J Infect Dis ; 227(10): 1132-1142, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-36821723

RESUMO

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), a dermal form of the disease, occurs in some visceral leishmaniasis (VL) patients following treatment. The PKDL disease mechanism is not yet clearly understood. Here we have studied the role of dermal fibroblasts in VL and PKDL disease mechanism. METHODS: Dermal fibroblasts were grown from skin biopsy explants collected from individual VL and PKDL patients and healthy controls. Fibroblasts from the third passage were subjected to RNA sequencing to analyze differentially expressed genes (DEGs). Significantly important genes were further validated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Transcriptome analysis of PKDL versus VL identified 516 DEGs (263 were overrepresented and 253 were underrepresented in PKDL). Among the top hub genes, MMP2, IL1B, CXCL8, IFIH1, NFKB1A, IL6, ISG15, and EGFR were underexpressed and ACTB, HSP90AA1, RAB7A, and RPS27A were overexpressed in PKDL compared to VL. CONCLUSIONS: Our data indicate that PKDL fibroblasts may present antigens through the MHC I pathway activating CD8+ T-cell mediated response, while VL fibroblasts express nuclear factor-κB (NFκB)-mediated chemokines, IL1B, IL6, and IL8, resulting in the recruitment of natural killer (NK)-cells and monocytes to the site of infection, leading to the clearance of parasite from the skin and visceralization of the disease.


Assuntos
Leishmania donovani , Leishmaniose Cutânea , Leishmaniose Visceral , Humanos , Leishmaniose Cutânea/parasitologia , Interleucina-6/genética , Expressão Gênica , Perfilação da Expressão Gênica , Índia
11.
Crit Rev Biotechnol ; 43(1): 142-169, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34957903

RESUMO

Bone metabolism constitutes the intricate processes of matrix deposition, mineralization, and resorption. Any imbalance in these processes leads to traumatic bone injuries and serious disease conditions. Therefore, bone remodeling plays a crucial role during the regeneration process maintaining the balance between osteoblastogenesis and osteoclastogenesis. Currently, numerous phytobiologics are emerging as the new therapeutics for the treatment of bone-related complications overcoming the synthetic drug-based side effects. They can either target osteoblasts, osteoclasts, or both through different mechanistic pathways for maintaining the bone remodeling process. Although phytobiologics have been widely used since tradition for the treatment of bone fractures recently, the research is accentuated toward the development of osteogenic phytobioactives, constituent-based drug designing models, and efficacious delivery of the phytobioactives. To achieve this, different plant extracts and successful isolation of their phytoconstituents are critical for osteogenic research. Hence, this review emphasizes the phytobioactives based research specifically enlisting the plants and their constituents used so far as bone therapeutics, their respective isolation procedures, and nanotechnological interventions in bone research. Also, the review enlists the vast array of folklore plants and the newly emerging nano-delivery systems in treating bone injuries as the future scope of research in the phytomedicinal orthopedic applications.


Assuntos
Remodelação Óssea , Osteoclastos , Osteoclastos/metabolismo , Osteogênese , Osteoblastos/metabolismo , Extratos Vegetais/farmacologia , Diferenciação Celular
12.
Dalton Trans ; 51(41): 15659-15668, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36222417

RESUMO

The photophysical properties of the anthracene appended koneramines (LAn) were analyzed and utilized as a chemosensor for the selective detection of Cd2+ and Zn2+. The complexation-induced inhibition of PET (photo-induced electron transfer) from the chelating nitrogen atoms to the excited state of the anthracene moiety resulted in a fluorescence "turn-on" signal upon binding with Cd2+ and Zn2+. The confocal microscopic imaging studies performed on the MCF-7 cells validated that the compound is potentially useful for detecting Cd2+ and Zn2+ inside the cells. The cadmium complex exhibited unique bactericidal activity against clinically relevant human pathogens. The excellent activity against multidrug-resistant S. aureus makes the complex useful as a new, easily synthesizable antibiotic. The cadmium complex LAnCdCl2 was not cytotoxic against vero cells with a selectivity index of 40, exhibited concentration dependent bactericidal killing, was non-interactive with several other clinically approved standard drugs, exhibited prolonged post-antibiotic effect (PAE) against S. aureus ATCC 29213 and possesses antibiofilm activity.


Assuntos
Cádmio , Staphylococcus aureus Resistente à Meticilina , Chlorocebus aethiops , Animais , Humanos , Cádmio/química , Staphylococcus aureus , Zinco/química , Células Vero , Antibacterianos/farmacologia , Antibacterianos/química , Antracenos , Nitrogênio
13.
Natl J Maxillofac Surg ; 13(1): 147-152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911814

RESUMO

Impacted maxillary canine is frequently encountered in clinical practice. Being the cornerstone of the dentition, orthodontic traction of impacted canine is always desirable in order to achieve successful functional occlusion. The aim of this case series is to illustrate different methods employed for orthodontic traction of maxillary impacted canine.

14.
Microbiol Spectr ; 10(4): e0165822, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35913202

RESUMO

Candida albicans is the leading cause of endogenous fungal endophthalmitis; however, its pathobiology studies are limited. Moreover, the contribution of host factors in the pathogenesis of Candida endophthalmitis remains unclear. In the present study, we developed a murine model of C. albicans endogenous endophthalmitis and investigated the molecular pathobiology of ocular candidiasis and blood-retinal barrier permeability. Our data show that intravenous injection of C. albicans in immunocompetent C57BL/6 mice led to endogenous endophthalmitis without causing mortality, and C. albicans was detected in the eyes at 3 days postinfection and persisted for up to 10 days. The intraocular presence of C. albicans coincided with a decrease in retinal function and increased expression of inflammatory mediators (tumor necrosis factor alpha [TNF-α], interleukin 1ß [IL-1ß], MIP2, and KC) and antimicrobial peptides (human ß-defensins [hBDs] and LL37) in mouse retinal tissue. C. albicans infection disrupted the blood-retinal barrier (BRB) by decreasing the expression of tight junction (ZO-1) and adherens junction (E-cadherin, N/R-cadherin) proteins. In vitro studies using human retinal pigment epithelial (ARPE-19) cells showed time-dependent activation of eIF2α, extracellular signal-related kinase (ERK), and NF-κB signaling and decreased activity of AMP-activated protein kinase (AMPK) leading to the induction of an inflammatory response upon C. albicans infection. Moreover, C. albicans-infected cells exhibited increased cellular permeability coinciding with a reduction in cellular junction proteins. Overall, our study provides new insight into the molecular pathogenesis of C. albicans endogenous endophthalmitis. Furthermore, the experimental models developed in the study can be used to identify newer therapeutic targets or test the efficacy of drugs to treat and prevent fungal endophthalmitis. IMPORTANCE Patients with candidemia often experience endophthalmitis, a blinding infectious eye disease. However, the pathogenesis of Candida endophthalmitis is not well understood. Here, using in vivo and in vitro experimental models, we describe events leading to the invasion of Candida into the eye. We show that Candida from the systemic circulation disrupts the protective blood-retinal barrier and causes endogenous endophthalmitis. Our study highlights an important role of retinal pigment epithelial cells in evoking innate inflammatory and antimicrobial responses toward C. albicans infection. This study allows a better understanding of the pathobiology of fungal endophthalmitis, which can lead to the discovery of novel therapeutic targets to treat ocular fungal infections.


Assuntos
Candidíase , Endoftalmite , Infecções Oculares Fúngicas , Animais , Barreira Hematorretiniana/microbiologia , Barreira Hematorretiniana/patologia , Candida , Candida albicans , Endoftalmite/tratamento farmacológico , Endoftalmite/microbiologia , Endoftalmite/patologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pigmentos da Retina/uso terapêutico
15.
ACS Appl Mater Interfaces ; 14(22): 25135-25146, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35613701

RESUMO

N95 respirator face masks serve as effective physical barriers against airborne virus transmission, especially in a hospital setting. However, conventional filtration materials, such as nonwoven polypropylene fibers, have no inherent virucidal activity, and thus, the risk of surface contamination increases with wear time. The ability of face masks to protect against infection can be likely improved by incorporating components that deactivate viruses on contact. We present a facile method for covalently attaching antiviral quaternary ammonium polymers to the fiber surfaces of nonwoven polypropylene fabrics that are commonly used as filtration materials in N95 respirators via ultraviolet (UV)-initiated grafting of biocidal agents. Here, C12-quaternized benzophenone is simultaneously polymerized and grafted onto melt-blown or spunbond polypropylene fabric using 254 nm UV light. This grafting method generated ultrathin polymer coatings which imparted a permanent cationic charge without grossly changing fiber morphology or air resistance across the filter. For melt-blown polypropylene, which comprises the active filtration layer of N95 respirator masks, filtration efficiency was negatively impacted from 72.5 to 51.3% for uncoated and coated single-ply samples, respectively. Similarly, directly applying the antiviral polymer to full N95 masks decreased the filtration efficiency from 90.4 to 79.8%. This effect was due to the exposure of melt-blown polypropylene to organic solvents used in the coating process. However, N95-level filtration efficiency could be achieved by wearing coated spunbond polypropylene over an N95 mask or by fabricating N95 masks with coated spunbond as the exterior layer. Coated materials demonstrated broad-spectrum antimicrobial activity against several lipid-enveloped viruses, as well as Staphylococcus aureus and Escherichia coli bacteria. For example, a 4.3-log reduction in infectious MHV-A59 virus and a 3.3-log reduction in infectious SuHV-1 virus after contact with coated filters were observed, although the level of viral deactivation varied significantly depending on the virus strain and protocol for assaying infectivity.


Assuntos
Compostos de Amônio , Vírus , Antivirais/farmacologia , Máscaras , Respiradores N95 , Polímeros/farmacologia , Polipropilenos
16.
Nanomedicine (Lond) ; 17(4): 255-270, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35109687

RESUMO

Recent advancements in biomedical tissue engineering are gaining wide interest. Implementing biology of living cells and organisms using technological solutions such as incorporating 4D printing and bioprinting for tissue regeneration/tissue repair, organ regeneration, early diagnosis of deadly diseases (particularly cancer, cardiac disorders and tuberculosis) has successfully opened a new generation of biomedical research. The present review primarily addresses the clinical application of 4D printing and bioprinting techniques for applications such as early detection of diseases and drug delivery. Notably, this review continues the discussion from part I regarding published informative data, in vitro and in vivo findings, commercial biosensors for early disease diagnosis, drug delivery and current challenges in 4D printing/bioprinting.


Assuntos
Bioimpressão , Nanomedicina , Bioimpressão/métodos , Atenção à Saúde , Impressão Tridimensional , Engenharia Tecidual/métodos
17.
Ocul Surf ; 23: 184-194, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583089

RESUMO

PURPOSE: SARS-CoV-2 RNA has been detected in ocular tissues, but their susceptibility to SARS-CoV-2 infection is unclear. Here, we tested whether SARS-CoV-2 can infect human conjunctival epithelial cells (hCECs) and induce innate immune response. METHODS: Conjunctival tissue from COVID-19 donors was used to detect SARS-CoV-2 spike and envelope proteins. Primary hCECs isolated from cadaver eyes were infected with the parental SARS-CoV-2 and its beta variant of concern (VOC). Viral genome copy number, and expression of viral entry receptors, TLRs, interferons, and innate immune response genes were determined by qPCR. Viral entry receptors were examined in hCECs and tissue sections by immunostaining. Spike protein was detected in the cell culture supernatant by dot blot. RESULTS: Spike and envelope proteins were found in conjunctiva from COVID-19 patients. SARS-CoV-2 infected hCECs showed high viral copy numbers at 24-72h post-infection; spike protein levels were the highest at 24hpi. Viral entry receptors ACE2, TMPRSS2, CD147, Axl, and NRP1 were detected in conjunctival tissue and hCECs. SARS-CoV-2 infection-induced receptor gene expression peaked at early time points post-infection, but gene expression of most TLRs peaked at 48 or 72hpi. SARS-CoV-2 infected hCECs showed higher expression of genes regulating antiviral response, RIG-I, interferons (α, ß, & λ), ISG15 & OAS2, cytokines (IL6, IL1ß, TNFα), and chemokines (CXCL10, CCL5). Compared to the parental strain, beta VOC induced increased viral copy number and innate response in hCECs. CONCLUSIONS: Conjunctival epithelial cells are susceptible to SARS-CoV-2 infection. Beta VOC is more infectious than the parental strain and evokes a higher antiviral and inflammatory response.


Assuntos
COVID-19 , SARS-CoV-2 , Antivirais , Células Epiteliais , Humanos , Imunidade Inata , RNA Viral
18.
Eur J Med Chem ; 226: 113839, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536668

RESUMO

Alkaloids are one of the most important classes of plant bioactives. Among these isoquinoline alkaloids possess varied structures and exhibit numerous biological activities. Basically these are biosynthetically produced via phenylpropanoid pathway. However, occasionally some mixed pathways may also occur to provide structural divergence. Among the various biological activities anticancer, antidiabetic, antiinflammatory, and antimicrobial are important. A few notable bioactive isoquinoline alkaloids are antidiabetic berberine, anti-tussive codeine, analgesic morphine, and muscle relaxant papaverine etc. Berberine is one of the most discussed bioactives from this class possessing broad-spectrum pharmacological activities. Present review aims at recent updates of isoquinoline alkaloids with major emphasis on berberine, its detailed chemistry, important biological activities, structure activity relationship and implementation in future research.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Hipoglicemiantes/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Berberina/química , Berberina/metabolismo , Humanos , Hydrastis/química , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Estrutura Molecular
19.
J Ayurveda Integr Med ; 12(3): 506-513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34376352

RESUMO

BACKGROUND: Nishamalaki is an Ayurvedic herbal formulation used to treat type 2 diabetes mellitus (T2DM), comprises Emblica officinalis and Curcuma longa. OBJECTIVE(S): One of the main cause of T2DM is Insulin Resistance (IR) hence, this study was planned to evaluate IR lowering effect of a standardized Nishamalaki extract "EmbliQur" in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM rats. MATERIALS AND METHODS: Curcuminoids (23.89% w/w), gallic acid (5.27% w/w) and tannins (25.44% w/w) were quantified from EmbliQur. Rats were fed HFD throughout the study of 45 days and received STZ (40 mg/kg, i.p) on the 15th day of the study. Rats with more than 250 mg/dl of fasting blood glucose level (FBGL) were considered diabetic and selected for administration of EmbliQur (500 mg and 1000 mg/kg) or the standard drug metformin (120 mg/kg, p.o) from the 18th day of the study for the next 27 days. FBGL and insulin levels of all rats were measured weekly and an oral glucose tolerance test (OGTT) was done at the end of the study. The values of FBGL and insulin were used to calculate IR by the HOMA-IR, QUICKI and Matsuda methods. RESULTS: Rats treated with STZ/HFD had significantly higher than normal FBGL and insulin levels throughout the study and exhibited skewed IR indices in the above three methods of IR assessment. EmbliQur treatment successfully lowered the HFD/STZ-elevated BGL and insulin levels, and ameliorated IR in all models of IR evaluation. CONCLUSION: EmbliQur 1000 mg/kg was noted to be more effective than EmbliQur 500 mg/kg in alleviating IR.

20.
Biomolecules ; 11(5)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069869

RESUMO

Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1ß) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.


Assuntos
Antivirais/farmacologia , Povidona-Iodo/farmacologia , Vírus de RNA/fisiologia , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular , Vírus Chikungunya/fisiologia , Chlorocebus aethiops , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/virologia , SARS-CoV-2/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero , Zika virus/fisiologia
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