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1.
Med Mol Morphol ; 52(1): 36-43, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29959534

RESUMO

Non-alcoholic steatohepatitis (NASH) is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, and hepatocyte injury with or without fibrosis. In this study, we explored the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor, on the progression of steatohepatitis in a murine model of NASH with diabetes. A novel NASH model with diabetes was generated by administration of streptozotocin injection to neonatal C57BL/6 mice (2-3 days old) combined with a high-fat diet feeding from the age of 4 weeks. The plasma biochemical parameters, oxidative stress, inflammation and histopathological changes were assessed. APD668 alone showed reduction in plasma glucose (- 39%, P < 0.05) and triglyceride level (- 26%) whereas a combined treatment of APD668 with linagliptin resulted in a more pronounced reduction in plasma glucose (- 52%, P < 0.001) and triglyceride (- 50%, P < 0.05) in NASH mice. In addition, co-administration of APD668 with linagliptin demonstrated a significant decrease in hepatic triglyceride, NAS score, hepatic TBARS and hepatic TNF-α in NASH mice with diabetes. These findings suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of NASH.


Assuntos
Diabetes Mellitus Experimental/complicações , Linagliptina/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Pirazóis/farmacologia , Pirimidinas/farmacologia , Animais , Dieta Hiperlipídica , Inibidores da Dipeptidil Peptidase IV/farmacologia , Progressão da Doença , Fibrose , Inflamação , Linagliptina/uso terapêutico , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Receptores Acoplados a Proteínas G/agonistas
2.
Toxicol Mech Methods ; 29(5): 334-343, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30588862

RESUMO

Para-methoxycinnamic acid (PMCA) and Ethyl-p-methoxycinnamate (EPMC) are reported to possess neuroprotective effect in reversing an acute memory deficit. However, there is a dearth of evidence for their therapeutic effect in chronic memory deficit. Thus, there is a scope to study these derivatives against the chronic model of cognitive dysfunction. The present study was aimed to determine the cognitive enhancing activity of PMCA and EPMC in aluminum-induced chronic dementia. Cognitive enhancing property of PMCA and EPMC was assessed using Morris water maze by analyzing spatial memory parameters such as escape latency, D-quadrant latency, and island entries. To find a possible mechanism, the effect of test compounds on altered acetylcholinesterase (AChE) activity and oxidative stress was determined in the hippocampus and frontal cortex of rats. Docking interaction of these derivatives with acetylcholinesterase enzyme and glutamate receptors was also studied. Treatment with PMCA and EPMC showed a significant improvement in spatial memory markers and altered hippocampal AChE activity in rats with cognitive dysfunction. The implication of hippocampal and cortical oxidative stress in memory impairment was confirmed with decreased catalase/increased thiobarbituric acid reactive substances (TBARS) in rats. PMCA and EPMC reversed the oxidative stress in the brain by negatively affecting TBARS levels. Against depleted catalase levels, PMCA was more effective than EPMC in raising the depleted catalase levels. In silico analysis revealed poor affinity of EPMC and PMCA with AChE enzyme and glutamate receptor. To conclude, PMCA and EPMC exerted cognitive enhancing property independent of direct AChE and glutamate receptor inhibition.


Assuntos
Alumínio/toxicidade , Cinamatos/farmacologia , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Memória Espacial/efeitos dos fármacos
3.
Biochem Biophys Res Commun ; 495(2): 1608-1613, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29203247

RESUMO

Non-Alcoholic SteatoHepatitis (NASH) is the more severe form of Non-Alcoholic Fatty Liver Disease (NAFLD) and is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, hepatocyte injury with or without fibrosis. Recently, GPR119 receptor has emerged as a novel therapeutic target for the treatment of dyslipidemia and non-alcoholic steatohepatitis. In the present study, we investigated the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor on the progression of steatohepatitis in mice fed on a high trans-fat diet. In this study, monotherapy with either APD668 or linagliptin caused a reduction in the levels of ALT, AST, glucose, cholesterol and epididymal fat mass but the effect was more pronounced upon treatment with combination of both drugs. On the other hand, combined treatment of APD668 with linagliptin demonstrated a non-significant additive effect in reduction of hepatic triglyceride (-78%) and cholesterol (-56%) compared to monotherapy groups. Moreover, co-administration of APD668 and linagliptin resulted in enhanced levels of active GLP-1 with additional benefit of significant synergistic decrease in body weight gain (-19%) in mice. We speculated that the enhanced effect observed with the combination treatment could be due to either 1) direct activation of GPR119 receptors present in liver and intestine or 2) enhanced active GLP-1 levels or 3) decreased degradation of GLP-1 in-vivo through DPPIV inhibition. Therefore, these findings clearly suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of non-alcoholic steatohepatitis.


Assuntos
Linagliptina/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Modelos Animais de Doenças , Progressão da Doença , Sinergismo Farmacológico , Quimioterapia Combinada , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Aumento de Peso/efeitos dos fármacos
4.
Oral Health Prev Dent ; 16(2): 169-174, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736496

RESUMO

PURPOSE: To assess and compare the salivary pH reversal phenomenon and calcium concentration in subjects consuming paneer and cheese after an acidogenic challenge and also to compare the salivary pH measurements using pH strips and a portable pen-type pH meter. MATERIAL AND METHODS: Sixty caries free undergraduate students were randomly selected and divided into two group: 1. paneer; 2. cheese. After determining the resting salivary pH using pH strips and a pen-type pH meter, participants were subjected to an acidogenic challenge (10% sucrose). Following consumption of test foods (10-gram cubes), salivary pH was measured at intervals of 5, 10, 15, 30 and 60 min to record the time taken for the salivary pH to return to baseline. Colorimetric salivary calcium concentration was estimated (Biochemical Analyzer) at baseline and after 60 min of test food consumption. The statistical tests used were Shapiro-Wilk's test for normality, repeated measures ANOVA, and the independent t-test. RESULTS: Test meals reversed the fall in pH after acidogenic challenge starting at 5 min and returning to baseline values after 30 min in both groups (p = 1.000). Colorimetric estimates showed higher salivary calcium concentrations with paneer (p < 0.001). The pen-type pH meter showed superior efficiency in terms of time (p < 0.001) compared to pH strips. CONCLUSION: The salivary pH reversal phenomenon was evident after consumption of both paneer and cheese following the acidogenic challenge. Consumption of paneer significantly increased salivary calcium concentration. The pen-type pH meter proved to be more efficient.


Assuntos
Cálcio/análise , Queijo , Laticínios , Dieta , Saliva/química , Adolescente , Cárie Dentária/prevenção & controle , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Adulto Jovem
5.
Oral Health Prev Dent ; 15(5): 453-459, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28785747

RESUMO

PURPOSE: The aim of this study was to determine the changes of salivary flow rate, pH, buffering capacity, total antioxidant capacity and changes in streptococci and lactobacilli counts at baseline, 1 month and 6 months of fixed orthodontic treatment. MATERIALS AND METHODS: An unstimulated salivary sample was collected from 30 out of 43 patients who were in need of fixed orthodontic treatment (mean age 17.8 ± 5.01 years). Salivary samples were collected from the patients before the placement of fixed orthodontic appliance (Gemini MBT 0223M) at 1 month and 6 months following start of the treatment. Samples were tested for significant changes in flow rate, pH, buffering capacity, total antioxidant capacity and streptococci and lactobacilli counts. Results were compared using ANOVA. RESULTS: The study results showed that orthodontic appliances significantly changed the unstimulated salivary flow rate (p < 0.05) (baseline: 0.40 ± 0.11, 1 month: 0.45 ± 0.09, 6 months: 0.44 ± 0.07) and buffering capacity (p < 0.05) (baseline: 5.01 ± 0.50,1 month: 3 .98 ± 0.78, 6 months: 4.02 ± 0.78) at the end of 1 month and 6 months whereas lactobacilli count showed significant changes at the end of 6 months (p < 0.05) (baseline: 6.20 ± 2.07, 1 month: 7.09 ± 3.78, 6 months: 7.85 ± 1.88). The pH, total antioxidant capacity and streptococci counts did not show any significant changes during the study period. CONCLUSION: It appears that 6 months of treatment with fixed orthodontic appliance resulted in a significant increase in unstimulated salivary flow rate and lactobacilli counts, whereas buffering capacity decreased significantly during the study period.


Assuntos
Lactobacillus/isolamento & purificação , Má Oclusão/terapia , Aparelhos Ortodônticos , Saliva , Streptococcus/isolamento & purificação , Adolescente , Feminino , Humanos , Estudos Longitudinais , Masculino , Boca/microbiologia , Saliva/química , Saliva/microbiologia , Saliva/fisiologia , Fatores de Tempo
6.
ScientificWorldJournal ; 2014: 802701, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24616646

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of gastrointestinal tract of immune, genetic, and environmental origin. In the present study, we examined the effects of sesamol (SES), which is the active constituent of sesame oil in the acetic acid (AA) induced model for IBD in rats. METHODS: The groups were divided into normal control, AA control, SES, and sulfasalazine (SS). On day 7, the rats were killed, colon was removed, and the macroscopic, biochemical, and histopathological evaluations were performed. RESULTS: The levels of MPO, TBARS, and tissue nitrite increased significantly (P < 0.05) in the AA group whereas they reduced significantly in the SES and SS treated groups. Serum nitrite levels were found to be insignificant between the different groups. CONCLUSIONS: The mucosal protective effects of sesamol in IBD are due to its potential to reduce the myeloperoxidase and nitrite content.


Assuntos
Ácido Acético/toxicidade , Benzodioxóis/uso terapêutico , Colo/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Peroxidase/metabolismo , Fenóis/uso terapêutico , Animais , Benzodioxóis/farmacologia , Colo/enzimologia , Feminino , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/enzimologia , Fenóis/farmacologia , Ratos , Ratos Wistar
7.
3 Biotech ; 14(4): 124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566928

RESUMO

Cases of diabetes are significantly increasing year by year, attracting the attention of medical professionals and researchers to focus on diabetes and its underlying complications. One among such are diabetic wounds which are difficult to heal, creating severe implications in the day-to-day chores of not only patients, but also family members. Dehydrozingerone (DHZ) is known to possess various effects like anti-inflammatory, anti-microbial, antioxidant, and wound-healing properties. The effect of DHZ on different phases of diabetic wound healing remains untested. Hence, this study was proposed to find out the effect of oral and topical formulation of DHZ on day 5, 10 and 15 of diabetic wound healing. Excisional wounds were created on the dorsal side of animals using punch biopsy to mimic human diabetic wounds. Topical DHZ gel (100 mg in 1 gm of gel) was prepared using 1% Carbopol 934 and was applied twice a day. The treated groups had increased percentage of wound closure; western blotting suggested that DHZ significantly increased ERK and JNK levels and decreased TNF and MMP 2 and 9 levels. From histopathological studies, it was observed that angiogenesis, collagen formation, granulation tissue formation, and fibroblast proliferation were improved on days 5, 10, and 15 of diabetic wound healing. These findings indicate that DHZ (both systemic and topical) are effective during the early phases of wound healing which gets impaired in diabetic wounds. Dehydrozingerone accelerated diabetic wound healing by regulating the various hallmarks of wound healing process.

8.
JMIR Res Protoc ; 13: e51087, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042887

RESUMO

BACKGROUND: Silver diamine fluoride (SDF) is becoming more widely recognized as a simple, cost-effective approach to minimize sensitivity and arrest caries. However, SDF results in caries that are stained black. Potassium iodide (KI) treatment with SDF may minimize or lessen the staining. However, the effectiveness of KI on staining has not been investigated. Studies demonstrating that potassium iodide reduces the black staining are still insufficient. This paper presents the study protocol for Healthy Smiles, a randomized controlled trial implemented to compare the staining propensity of SDF and SDF+KI. OBJECTIVE: This study, Healthy Smiles, aims to evaluate the staining propensity of SDF and SDF+KI using a Nix Mini color sensor among children aged 4 to 6 years. Another objective of the study is to evaluate the caries-arresting effect of SDF and SDF+KI in the treatment of carious primary teeth. METHODS: This study is a randomized controlled trial. A total of 60 children with caries that meet the criteria of the International Caries Detection and Assessment System (code 1 or above) will be randomly assigned to treatment groups, where group 1 will be treated with SDF and group 2 will be treated with SDF+KI. Discoloration of treated lesions will be assessed digitally using a Nix Mini color sensor. Participants will be followed up at 1, 3, and 6 months after treatment to digitally record the ∆L and ∆E values using the Nix Mini color sensor. Data will be analyzed using SPSS (version 28; IBM Corp). Independent sample t tests and the Mann-Whitney U test will be used to compare the 2 groups. RESULTS: Enrollment started in October 2023. It is estimated that the enrollment period will be 12 months. Data collection is planned to be completed in 2024. CONCLUSIONS: The presented paper describes Happy Smiles, a project that provides an opportunity to address the aesthetic inconvenience of patients without compromising the effectiveness of the SDF treatment. The trial findings will contribute to the limited evidence base related to discoloration after SDF intervention to improve aesthetic appearances in child oral health. If the results from the trial are promising, it will lead to the development of a model for child oral health and pave the way for further research in child oral health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51087.


Assuntos
Cárie Dentária , Fluoretos Tópicos , Iodeto de Potássio , Compostos de Amônio Quaternário , Compostos de Prata , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Cariostáticos/administração & dosagem , Cariostáticos/farmacologia , Cárie Dentária/prevenção & controle , Fluoretos Tópicos/administração & dosagem , Fluoretos Tópicos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Descoloração de Dente/tratamento farmacológico , Descoloração de Dente/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
BMC Complement Altern Med ; 13: 127, 2013 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-23742226

RESUMO

BACKGROUND: Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. METHODS: Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. RESULTS: TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. CONCLUSION: The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.


Assuntos
Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Terminalia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono , Caspase 3/metabolismo , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Hepatócitos/efeitos dos fármacos , Humanos , Fígado/enzimologia , Masculino , Camundongos , Casca de Planta , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Terminalia/efeitos adversos
10.
J Basic Clin Physiol Pharmacol ; 34(2): 125-136, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34751526

RESUMO

Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons' development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer's disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus' BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.


Assuntos
Doença de Alzheimer , Fator Neurotrófico Derivado do Encéfalo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Cognição
11.
Cureus ; 15(3): e36324, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37077594

RESUMO

Because of their complex epidemiology and etiology, cervical abrasions usually manifest with concealing symptoms. The buccolingual dimension of the sore is considered the most important metric to rank the damage and evaluate its long-term prognosis. In this piece, we will break this down and offer the Cervical Abrasion Index of Treatment Needs (CAITN), a simple grouping structure based on the clinical presentation of the sore that may be used to establish a basic, useful, treatment-based order. CAITN is the practical approach to routine screening and recording cervical abrasion lesions. The index provides epidemiologists, public health professionals, and practitioners with a practical means of assessing the treatment needs (TN) of cervical abrasion.

12.
Cureus ; 15(1): e33471, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36756019

RESUMO

Objective This study was intended to compare the mean buccolingual measurement of abraded teeth with/without sensitivity. The hypothesis was that the suggested treatment approaches would be in agreement with that of the treatment needs (TN) elicited using the Cervical Abrasion Index of Treatment Needs (CAITN) probe and aid in the development of a prospective CAITN index for clinical/community studies of effective therapeutic measures. Materials and methods  A cross-sectional study was carried out on 30 individuals with a mean age of 48.4±12.54 years, comprising 840 teeth with/without cervical abrasion. The buccolingual measurement of each tooth was recorded using the CAITN probe. The response to air-blast was assessed by a short blast of one-second duration at a distance of 1 cm for each tooth. An endodontist was also asked to indicate the treatment methods used by him for the treatment of abrasions. His opinions regarding the TN were later compared with the data collected by an investigator. Results The mean buccolingual measurements of all the teeth were compared with the dentinal sensitivity using the independent t-test and were statistically highly significant. Furthermore, one-way analysis of variance disclosed that there was a statistically highly significant difference found for all the TN (p<0.01) such as none, preventive, basic, and advanced restorative TN followed by Tukey honestly significant difference post hoc tests for multiple pair-wise comparisons. The running receiver operator characteristic curve discloses the best cut-off value of the buccolingual measurement to predict the various categories of TN of each tooth. As the area under the curve is more close to 1 (noticed in the majority of the teeth in the sample), the model predicts the TN more precisely based on the buccolingual measurements. Conclusion The present study enables a correct diagnosis of cervical abrasions and determines the various TN with the most appropriate restorative material. These baseline data help to design clinical studies that test relevant treatment and diagnostic strategies.

13.
J Basic Clin Physiol Pharmacol ; 34(2): 137-150, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34995024

RESUMO

Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/terapia , Pé Diabético/diagnóstico , Cicatrização
14.
J Cell Commun Signal ; 17(3): 673-688, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36280629

RESUMO

INTRODUCTION: One of the most common problems of diabetes are diabetic foot ulcers (DFUs). According to National Institute for Health, initial management of DFUs can decrease the complication of limb amputations and can improve the patient's quality of life. DFU treatment can be optimized with the help of multidisciplinary approach. Based on many studies, control of glucose levels in blood, antioxidant activity, reduction in cytokine levels, re-epithelialization, collagen formation, migration of fibroblasts are major phases involved in managing DFU. Dehydrozingerone (DHZ), has been known for its anti-inflammatory, antioxidant and wound healing properties. METHODOLOGY: Three months high-fat diet and low dose of streptozotocin-induced type-II diabetic foot ulcer model was used to evaluate the effectiveness of dehydrozingerone. DHZ was given orally to rats for 15 days post wounding. TNF-α, IL-1ß and antioxidant parameters like lipid peroxidation, glutathione reductase were estimated. Immunoblotting was done to investigate the effect of DHZ on the expression of ERK, JNK, HSP-27, P38, SIRT-1, NFκB, SMA, VEGF and MMP-9 in skin tissue. Histopathology was performed for analyzing DHZ effect on migration of fibroblasts, formation of epithelium, granulation tissue formation, angiogenesis and collagen formation. RESULTS: DHZ decreased the levels of malondialdehyde, TNF-α, IL-1ß and increased glutathione levels in wound tissue. Western blotting results suggested that DHZ activated ERK1/2/JNK/p38 signaling, increased expression of HSP-27, SIRT-1, VEGF, SMA thus facilitating the migration and proliferation of fibroblasts, angiogenesis and decreased inflammation. Masson Trichrome & histopathology showed an increase in collagen, epithelial and granulation tissue formation. CONCLUSION: DHZ significantly accelerates the healing of diabetic foot ulcers in high fat diet fed plus low dose streptozotocin induced type-II diabetic Wistar rats.

15.
Nanomedicine (Lond) ; 18(27): 2061-2080, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-38197397

RESUMO

Oral squamous cell carcinoma (OSCC) is an invasive and highly malignant cancer with significant morbidity and mortality. Existing treatments including surgery, chemotherapy and radiation have poor overall survival rates and prognosis. The intended therapeutic effects of chemotherapy are limited by drug resistance, systemic toxicity and adverse effects. This review explores advances in OSCC treatment, with a focus on lipid-based platforms (solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrids, cubosomes), polymeric nanoparticles, self-assembling nucleoside nanoparticles, dendrimers, magnetic nanovectors, graphene oxide nanostructures, stimuli-responsive nanoparticles, gene therapy, folic acid receptor targeting, gastrin-releasing peptide receptor targeting, fibroblast activation protein targeting, urokinase-type plasminogen activator receptor targeting, biotin receptor targeting and transferrin receptor targeting. This review also highlights oncolytic viruses as OSCC therapy candidates.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Nanopartículas , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Lipídeos/uso terapêutico
16.
F1000Res ; 12: 107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106650

RESUMO

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A needs to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions.


Assuntos
Isoflavonas , Neoplasias , Masculino , Feminino , Humanos , Isoflavonas/farmacologia , Glycine max , Neoplasias/tratamento farmacológico
17.
J Pharm Bioallied Sci ; 14(Suppl 1): S378-S383, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36110606

RESUMO

Introduction: The aim of this study was to analyze the anatomic crowns of the maxillary and mandibular dentition concerning the mesiodistal, buccolingual measurements which will be used to establish normative data as a part of comprehensive study being carried out to determine the depth of the cervical abrasion (CA) of the individuals by predicting the CA Index of Treatment Needs (CAITN) score. Materials and Methods: A newly developed instrument termed as CAITN probe was used to measure CA of the tooth more quantitatively. The mesiodistal and buccolingual width of all the 14 maxillary and mandibular teeth from the right second permanent molar to the left second permanent molar of the study sample was measured. The ratio between buccolingual and mesiodistal measurements of each tooth of the maxillary and mandibular arch of the study sample (n=100) was also determined. Statistical analysis was performed using the SPSS 26.0 software. Results: Descriptive statistics were calculated for each group independently. The statistical significance of the difference in mean in mesiodistal and buccolingual diameters between males and females was calculated using the t-test for independent samples with p < 0.05. The ratio was highest in the left second premolar (1.752) and least in the right central incisor (0.980) of the maxillary arch. Similarly, the ratio was highest in the left central incisor (1.723) and least in the left second molar (0.910) of the mandibular arch. Conclusion: The present study was conducted as an initial step in the process of development of the novel tool or index enabling the dentists to organize the health-care needs of their patients by facilitating standardized identification of CA with objective measurements used for epidemiological or community purpose.

18.
J Pharm Bioallied Sci ; 14(Suppl 1): S403-S409, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36110652

RESUMO

Background: Cervical abrasion is a multifactorial process due to the use of abrasive dentifrices along with improper brushing patterns. An extensive lesion may cause loss of structural integrity of tooth and esthetically unacceptable. The purpose of the study was to assess the prevalence of cervical abrasion with age, gender, and oral hygiene practices among workers in a spinning mill, Kerala. The study also aimed to identify the buccolingual measurements of each abraded tooth using the Community Abrasion Index of Treatment Needs (CAITN) probe. Materials and Methods: A cross-sectional study where 366 subjects (257 males and 109 females) above 20 years of age were selected using a random sampling technique. Data was collected from the assessment form comprising demographic data and oral hygiene practices of the subjects. Clinical examination for abrasion and buccolingual measurements of abraded tooth recorded using CAITN probe. The statistical analysis was done using SPSS 26.0. for calculating descriptive statistics, Chi-square test, and binary logistic regression. Results: The overall prevalence of abrasion was 37.2% and 97.7% of subjects with abrasion had sensitive teeth and were statistically significant. Age, gender (males) and combined horizontal and vertical method of brushing technique were strongly associated with the cervical lesion (P < 0.001). Binary logistic regression analysis showed that age group, gender, combined horizontal and vertical method of brushing, and presence of sensitive tooth was associated with the abrasion. Conclusion: It is concluded that the severity of the abrasion is an age-related phenomenon associated with combined horizontal and vertical strokes of brushing and is common among the male population. Dentinal hypersensitivity is also more prevalent with cervical abrasion. The novel CAITN probe can be used as an effective tool to assess the cervical abrasion and its treatment needs.

19.
J Pharm Bioallied Sci ; 14(Suppl 1): S384-S389, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36110716

RESUMO

Context: Although a common dental problem, there are no simple instruments or reliable methods to measure cervical abrasion. Aim: To study the design, development, calibration, efficacy, and compliance of usage of a novel Cervical Abrasion Index of Treatment Need (CAITN) probe to measure cervical abrasion. Settings and Design: The ex-vivo study was conducted as a part of comprehensive study for the development of standardized CAITN probe and index with a standard methodology for recording the abrasion. Materials and Methods: The compliance and usage of the probe were assessed by a standardized set of questionnaires to the interns followed by an ex-vivo study in 100 subjects. Gold standard comparisons with Vernier caliper, inter-examiner, and intra-examiner reliability were analyzed using SPSS. Results: Data from the questionnaire indicate that 100% of examiners had no difficulty in handling the instrument or measuring and reading the values. Comparison between the CAITN probe and the gold standard was statistically significant indicating a correlation for cervical abrasion measurement between the two methods (p < 0.001). The mean difference between the two measurements using the CAITN probe and gold standard method was calculated with paired t-test and was insignificant (p > 0.05). High statistical significant correlation was also found for intra-examiner and inter-examiner reliability measurement of CAITN probe (p < 0.001). Conclusion: The design and structure of the CAITN probe are standardized with a fair gold standard comparison and that the novel probe can be used as an effective tool to measure the depth of cervical abrasion and its treatment needs.

20.
Diabetes Metab Syndr ; 16(7): 102542, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35724488

RESUMO

BACKGROUND & AIM: Diabetic foot ulcers are major cause of lower limb amputations in the diabetic population. The major factors that play a role in causing the delay of the process of healing in diabetic foot ulcers broadly are decreased angiogenesis, reduced proliferation and migration of keratinocytes/fibroblasts. The typical wound healing process has four phases which are overlapping with each other thus making the healing even more complex. Hence it is essential to identify a therapeutic target that involves the regulation of the cellular factors involved in healing and helps to increase angiogenesis and can regulate all four phases accordingly. METHOD: Literature review involved a search of the databases namely, PubMed, Cochrane, EMBASE, and Web of Science database. Articles were identified and retrieved that specifically dealt with Notch as a target in healing of wounds and its mechanism of action on various cells and phases of healing. RESULTS: Notch is a cell surface receptor which interacts with transmembrane ligands of the nearby cells and is involved in cell proliferation, differentiation, cell fate and death. It is also involved in cell-to-cell communication, cell signaling, and various phases of development. There exist four known notch genes and five ligands which interact with notch proteins. Hyperglycemia plays a role in the activation of the notch receptor thus causing the release of inflammatory mediators via macrophages. As notch can regulate macrophage-mediated inflammation it can serve as a therapeutic target for diabetic foot ulcers. CONCLUSION: This review focuses on the effect of notch on various cell mediators and phases of diabetic wound healing and deals with how notch activation or inhibition can serve as a potential therapeutic target for healing diabetic foot ulcers.


Assuntos
Diabetes Mellitus , Pé Diabético , Amputação Cirúrgica , Pé Diabético/terapia , Humanos , Ligantes , Transdução de Sinais , Cicatrização/fisiologia
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