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1.
Biochem Biophys Res Commun ; 636(Pt 1): 89-95, 2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36332487

RESUMO

Nicotinamide adenine dinucleotide (NAD+), a biological molecule integral to redox reactions involved in multiple cellular processes, has the potential to treat nonalcoholic fatty liver diseases (NAFLDs) and nonalcoholic steatohepatitis (NASH). Nicotinamide mononucleotide adenylyltransferase (Nmnat1), one of the NAD+ biosynthesizing enzymes, plays a central role in all NAD+ metabolic pathways and it is vital to embryonic development. However, the function of Nmnat1 in metabolic pathology and, specifically, in the development and progression of NAFLD and NASH remains unexplored. First, we generated hepatic Nmnat1 knockout (H-Nmnat1-/-) mice to investigate the physiological function of Nmnat1 and found that NAD+ levels were significantly lower in H-Nmnat1-/- mice than control mice. However, H-Nmnat1-/- mice appeared normal with comparable metabolic activity. Next, we used three different diet-induced NASH models to assess the pathophysiological role of Nmant1 in metabolic disorders and discovered that hepatic loos of Nmnat1 decreased 35%-40% of total NAD+ in an obese state. Nevertheless, our analysis of phenotypic variations found comparable body composition, gene expression, and liver histology in all NASH models in H-Nmnat1-/- mice. We also found that aged H-Nmnat1-/- mice exhibited comparable liver phenotypes with control mice. These findings suggest that Nmnat1 has a redundancy to the pathophysiology of obesity-induced hepatic disorders.


Assuntos
Nicotinamida-Nucleotídeo Adenililtransferase , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , NAD/metabolismo , Fígado/metabolismo , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo , Obesidade/metabolismo , Dieta , Camundongos Endogâmicos C57BL
2.
Pak J Pharm Sci ; 34(5(Supplementary)): 1995-2002, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34836872

RESUMO

To explore complex biological and chemical systems, pharmaceutical research has effectively included several molecular modeling tools into a range of drug development initiatives. Molecular docking methods are widely employed in current drug design to investigate ligand conformations within macromolecular targets' binding sites. This method also estimates the ligand-receptor binding free energy by assessing critical phenomena involved in the intermolecular recognition process. In an attempt, several natural products have been synthesized in our laboratory. All the synthesized compounds containing (6H-Dibenzo[b,d]pyran-6-one) framework were subjected to molecular docking studies for the inhibition of CYP1B1 and BCL2 proteins using Auto Dock Vina software and the interacting amino acid residues were visualized using Discovery Studio, to look into the binding modalities that might influence their anticancer properties. The in silico molecular docking study outcomes showed that all the synthesized compounds having optimum binding energy and have a decent affinity to the active pocket, thus, they may be considered as a respectable inhibitor of CYP1B1 and BCL2 proteins.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzopiranos/síntese química , Benzopiranos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Sítios de Ligação , Simulação por Computador , Citocromo P-450 CYP1B1/antagonistas & inibidores , Desenho de Fármacos , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Receptores de Droga/efeitos dos fármacos
3.
Pak J Pharm Sci ; 33(2): 641-649, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32276910

RESUMO

Hyperuricemia is a common metabolic disorder and several herbal formulations are being used for its treatment. The study aimed to develop herbal formulation (Urinil B) and find its hypouricemic effects in vitro and in vivo. Urinil B was prepared by taking Trachyspermum ammi, Piper nigrum and Berberis vulgaris equally. In vitro Dissolution test and xanthine oxidase inhibition assay was performed for checking capsule absorbance and IC50 calculation respectively. For in vivo experimentation, the study comprised of 14 groups of rats (n=6). Results showed that significant xanthine oxidase inhibition was shown by herbal formulation with IC50 of 586±1.5µg/mL. Oral administration of Urinil B 250, 500 and 1000 mg/kg decreased serum and liver uric acid levels of hyperuricemic rats in dose and time dependent manner. 3 day and seven day administration of Urinil B reduced serum and liver uric acid level more significantly as compared to one day administration. However, allopurinol normalized serum and liver uric acid levels in all study groups. The present study indicated marked hypouricemic effects of Urinil B in hyperuricemia induced by potassium oxonate in rats. However, due to caveat of small sample size in this study, clear conclusion regarding hypouricemic potential of Urinil B can't be made.


Assuntos
Modelos Animais de Doenças , Desenvolvimento de Medicamentos/métodos , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Animais , Relação Dose-Resposta a Droga , Composição de Medicamentos/métodos , Supressores da Gota/isolamento & purificação , Hiperuricemia/induzido quimicamente , Hiperuricemia/metabolismo , Masculino , Ácido Oxônico/toxicidade , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Ácido Úrico/metabolismo
4.
J Ayub Med Coll Abbottabad ; 29(1): 45-49, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28712172

RESUMO

BACKGROUND: Morbid obesity has become a surgically treatable problem. Laparoscopic sleeve gastrectomy is becoming a popular choice both for surgeons and patients due to effectiveness and low complication rates. METHODS: It was a prospective case series spanning over 6 years. Patient enrolment started from January 2009 and data collection completed in January 2015. Patient with BMI (weight in kilogram/height in meter square) of more than 35 were included in the study. Follow up was at 2 weeks, 1 month, 6 months and 12 months. Success was defined as 25% of excess weight loss at 1 year. Paired t-test was used as a test of significance. RESULTS: A total of 34 patients were included in the study over a 6-year period, 3 were lost to follow up and one patient died of cardiac arrest. Data of 30 patients is considered for final analysis. Mean age was 39.5±10 years, while mean BMI 45.8±6.3 (range 37.1-62.2). Average weight of the patients preoperatively was 129.9±20.8 kg while mean excess weight was 70.3±20.8 kg. Average weight loss at two weeks was 8.9±2.9 kg, at one month 14.7±4.6 kg, at 6 months 25.0±7.6 kg and at twelve months was 31.4±6.8 kg. Mean percentage of excess weight loss after 2 weeks was 13.5±4.6%, at one month 22.0±6.1%, at six months 37.6±12.0% and at twelve months 47.3±10.1%. CONCLUSIONS: Laparoscopic sleeve gastrectomy is an effective weight loss surgery with minimal complications. On average weight loss of about 30 kg at one year was achieved which equals to almost half of excess body weight.


Assuntos
Gastrectomia , Laparoscopia , Obesidade Mórbida , Redução de Peso , Adulto , Seguimentos , Gastrectomia/métodos , Gastrectomia/estatística & dados numéricos , Humanos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Resultado do Tratamento
5.
Pak J Pharm Sci ; 29(2 Suppl): 657-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27113299

RESUMO

This study was conducted to evaluate the efficacy of Unani Ajmal06, an herbal formulation for management of chronic renal failure (CRF). The therapeutic evaluations of three different formulations such as Itrifal Kashneezi, Jawarsih Zarooni Sada medicines were conducted on number 35 CRF patients clinically diagnosed cases of chronic kidney failure. It was found that herbal coded Ajmal06 was effective for the treatment of CRF in 70% of the patients treated. SPSS tests on sign and symptoms indicated the efficacy of Ajmal06 in lowering serum creatinine level in 70% of patients of chronic renal failure. In clinical response of BUN exhibited 75% of patients improved where as in case of fatigue (70%), edema (90%), leg pain (76%) improved these types of conditions with significant p value.


Assuntos
Creatinina/sangue , Falência Renal Crônica/sangue , Medicina Unani , Adulto , Humanos , Adulto Jovem
6.
Pak J Pharm Sci ; 29(4): 1331-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27393456

RESUMO

HIV or AIDS is a major threat for humanity in the world especially in developing countries. The causative factor of the syndrome is HIV, which infects and destroys one of the cellular components of the immune system, the T cells, causing deficiency in the immunological surveillance and ultimately leading to AIDS. According to WHO, around 35 million people were living with HIV in 2013 and since the start of epidemic 39 million people have died due to AIDS. Center for disease control and prevention estimated in 2014 that 1,201,100 people aged 13 and above were suffering from HIV infection Worldwide. The most effective approach is the highly active antiretroviral therapy (HAART) containing the combined use of drugs having different mechanisms of action. However, complete eradication of HIV from the body does not occur by HAART, but it lead to long term toxicity occurs and emerges as drug resistant. Despite the recent development of various new antiretroviral compounds, there is still a need to develop need to search for new alternatives which are equally efficient and less expensive as compared to the contemporary treatment available. This review provides an overview and a summary of herbal medicines for HIV infection and summarized the efficacy and medicinal use of different plants used in the treatment of HIV infection. The objective of this review is to enlighten the recent advances in the exploration of medicinal plants used for treatment of HIV/AIDS.


Assuntos
Infecções por HIV/tratamento farmacológico , Fitoterapia , Plantas Medicinais , Terapia Antirretroviral de Alta Atividade , Humanos
7.
Pak J Pharm Sci ; 29(3): 919-27, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27166535

RESUMO

Hepatitis C virus (HCV) infection is a serious and significant global health problem in the Pakistan and elsewhere. In majority of cases HCV infection remains asymptomatic but in advance cases it may progress to fibrosis of liver, shrinkage of liver cells or failure of liver. The hepatitis C may progress to cause liver cirrhosis that mostly develop in 20% of the affected patients in 20 years with an increased risk in male, alcoholic drink, immune-compromised and who acquire HCV infection after the age of 40 years. This was an open-label prospective study conducted on 66 clinically and immunologically diagnosed cases of HCV infection. In Hepcinal treated group, there were significant improvement in HCV associated symptoms compared to control group (p<0.05). While Interferon therapy resulted in significant improvement in serological response (55.88%) compared to Hepcinal treated patients (46.88%). It was concluded that Hepcinal has shown better clinical response but no significant serological response (p=0.3244) and it might be an alternative therapy to treat hepatitis C infection and to prevent its progression into chronic ailment.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Preparações de Plantas/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Hepatite C/diagnóstico , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Paquistão , Preparações de Plantas/efeitos adversos , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
J Pak Med Assoc ; 65(11): 1228-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26564299

RESUMO

Gastro-Intestinal Stromal Tumours are rare tumours, constituting less than 1% of gastrointestinal tumours. They are the most common mesenchymal origin tumours of gastro-intestinal tract. Tyrosine kinase c-kit oncogene mutation is found in all cases. These tumours are sensitive to imatinib. They are usually noted incidentally on endoscopy or present with haematemesis after ulceration. We are reporting the laparoscopic resection of GIST in a 67 year old male who had presented with haematemesis. He was found to have a gastric polyp on endoscopy. Endoscopic ultra-soundshowed the tumour to be arising from the submucosa. Histo-pathology showed the tumour to be GIST. Patient is currently undergoing chemotherapy.


Assuntos
Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia , Idoso , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino
9.
J Pak Med Assoc ; 65(5): 565-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26028396

RESUMO

Laparoscopic Pancreatic Pseudocyst (PP) surgery can be performed via anterior or posterior cystogastrostomy, endoscopy-assisted surgery and cystojejunostomy. We conducted a prospective analysis of our patients undergoing laparoscopic cystogastrostomy to analyse the merits and demerits of the procedure. In a period of 3 years from January 2010 to December 2012 all the patients who underwent laparoscopic drainage of pancreatic pseudocysts were prospectively analysed. A total of 12 patients underwent a transgastric anterior cystogastrostomy with a stoma size of 4.5cms. There was no intraoperative or postoperative bleeding or leakage on anastomotic lines. Post-op pain score on the first post-op day was 4 (2-5) on the Visual Analogue Scale (VAS). Average hospital stay was 4.1±2.3 days. All patients had complete resolution of symptoms on follow-up. Follow-up computed tomography (CT) scans on 8 patients showed complete resolution of the cysts. Laparoscopic cystogastrostomy is a safe and feasible method and provides efficient drainage of PP.


Assuntos
Gastrostomia/métodos , Pseudocisto Pancreático/cirurgia , Adulto , Idoso , Estudos de Coortes , Drenagem/métodos , Feminino , Gastroscopia/métodos , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Paquistão , Estudos Prospectivos
10.
Pak J Pharm Sci ; 28(1): 43-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25553684

RESUMO

The topical herbal formulation Eezpain spray consisting of natural ingredients that have been clinically proved for its analgesic and anti-inflammatory activity. The designed formulation on application knee and wrist joints, back of neck and shoulder, forearms and lower back exhibited significant efficacy. A total of 20 subjects both male and female applied Eezpain spray consisting of Gaultheria oil, Eucalyptus oil, Turpentine oil, Clove Oil, Menthol and Camphor. All the active materials are cited that these have analgesic activity in myalgia and neuralgia. The study design was prospective and opens as pilot study followed the inclusion and exclusion criteria. All the sign and symptoms were noted at baseline and at the end of 14 days treatment performance was evaluated. The statistical analysis was done by using Microsoft Excel2007 and SPSS version 18.0. It is concluded that Eezpain spray has shown efficacy in mild to moderate cases on applying locally to the affected parts to relieve pain from different ailments.


Assuntos
Analgésicos/administração & dosagem , Mialgia/tratamento farmacológico , Preparações de Plantas/administração & dosagem , Administração Cutânea , Adulto , Aerossóis , Idoso , Artralgia/diagnóstico , Artralgia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/diagnóstico , Medição da Dor , Paquistão , Fitoterapia , Projetos Piloto , Plantas Medicinais , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
11.
Pak J Pharm Sci ; 28(6 Suppl): 2291-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26687746

RESUMO

Hypercholestriolemia is major risk factor that enhances the incidence of cardiovascular disease and coronary artery disease. The present study was conducted to normalize the lipid profile in the blood by using Biocor Plus for hypercholesterolemia compared with Simvastatin. It was prospective randomized case control study conducted on 70 diagnosed patients of hypercholesterolemia at Sohail Memorial Hospital, Karachi and Amir Habib Medical Center and Maternity Home, Karachi. Patients of both genders (30-70 years) with clinical diagnosis of Hypercholesterolemia. Sample sizes for this study included total of 70 subjects. There was statistically significant difference when comparing the effectiveness of test drug, Biocor Plus to control drug, Simvastatin for the treatment of primary hypercholesterolemia. This is clearly evident that the herbal coded test drug, Biocor Plus possesses a therapeutic value for the treatment of primary hypercholesterolemia. There were no untoward or significant side effects associated with the use of Biocor Plus that proved its good acceptability by the patients. Moreover there was subjective feeling of wellbeing regarding breathlessness and chest tightness or pressure in the patients taking Biocor Plus. This makes an interesting point to focus on this effective alternative drug for primary hypercholesterolemia.

12.
Pak J Pharm Sci ; 28(5): 1655-63, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26408885

RESUMO

Atopic dermatitis (AD) is defined as a chronic, highly pruritic inflammatory condition of skin. It is estimated that this disease may lead significant morbidity and also adversely affects the quality of life. Atopic dermatitis responds well to home treatment. Proper skin care reduces the need for medicines. Topical creams and oral antihistamines can be used to suppress the symptoms. The clinical trial was conducted on 60 patients in which 30 are control and 30 are test by taking written consent from them. Dermovix significantly improved skin symptoms associated with AD. This Dermovix ointment was safe and well tolerated in specified age group patients. Overall results of individual group were analyzed by using Paired sample t-test and level of significance of all the symptoms was calculated. Both the drugs showed similar efficacy and the calculated p value was p<0.05. Except in case of dry skin the test drug had shown not significant p value i.e. 0.407. When we compare all these and their effects and patients' complaints then Test group have shown better results because of no side effects.


Assuntos
Terapias Complementares , Dermatite Atópica/tratamento farmacológico , Medicina Herbária , Fitoterapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Fitoterapia/efeitos adversos
13.
Pak J Pharm Sci ; 28(3): 863-70, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26004718

RESUMO

This study was conducted to evaluate the role of Unani herbal drugs Pepsil and Safoof-e-katira on the gastro esophageal reflux disease (GERD). This was multicentre randomized case control study conducted at Matab Hakeem Muhammad Noor-ud-din, Burewala; Aziz Muhammad din Medical and Surgical Centre, Burewala and Shifa-ul-mulk Memorial Hospital, Hamdard University Karachi. The patients were selected according to inclusion and exclusion criteria. In test group-1 the male female ratio was 40%, 60%; test group-2 was 42%, 58% and in control group was 44%, 56% respectively. The observed symptoms in the study were increased appetite (TG-1-95%, TG-2-95% and CG-89%), difficulty in swallowing (TG-1-93%, TG-2-96% and TC-94%), belching/burping (TG-1-97%, TG-2-97% and CG-95%), vomiting (TG-1-90%, TG-2-96% and CG-89%), heart burn (TG-1-100%, TG-2-100% and CG-98%), palpitation (TG-1-100%, TG-2-100% and CG-97%), epigastric pain (TG-1-97%, TG-2-97% and CG-90%), abdominal cramps (TG-1-97%, TG-2-98% and CG-95%), tenesmus (TG-1-100%, TG-2-100% and CG-97%), flatulence (TG-1-100%, TG-2-75% and CG-95%), wakeup during sleep (TG-1-94%, TG-2-87% and CG-94%). The p-value of the results of the symptoms was 0.000 except flatulence where the value was 0.001. The statistical results of the study prescribed that all the drugs studied (Pepsil, Safoof-e-katira and Omeprazole) are highly significant. The herbal coded drug Pepsil showed no side effects and unani herbal drug safoof-e-katira showed minimum result of 75% in the patients while Omeprazole resulted with some side effects. In the result it can be concluded that the herbal coded drug Pepsil is a potent herbal drug for gastro esophageal reflux disease.


Assuntos
Transtornos de Deglutição/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Azia/tratamento farmacológico , Omeprazol/uso terapêutico , Fitoterapia , Preparações de Plantas/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Astragalus gummifer , Coriandrum , Transtornos de Deglutição/etiologia , Feminino , Refluxo Gastroesofágico/complicações , Azia/etiologia , Humanos , Masculino , Phyllanthus , Plantago , Tragacanto , Resultado do Tratamento
14.
Cell Rep ; 43(7): 114491, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002127

RESUMO

Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin's regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states.

15.
Heliyon ; 10(6): e27279, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545175

RESUMO

Euphorbia prostrata (E. prostrata) and Crotalaria burhia (C. burhia) are widely found in flora of the Cholistan Desert of Bahawalpur, Pakistan and are traditionally used to treat pain and chronic disease. The current study aimed to evaluate their phytochemical screening, antioxidant activity, in-vivo phagocytic activity, and analgesic activity. Both the plant extracts were investigated for phytochemical screening, Fourier Transform Infrared (FTIR) analysis, in-vitro antioxidant by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method, in-vivo immunomodulatory activity by macrophages phagocytosis using carbon clearance rate assay and analgesic activity by acetic acid produced writhing method. Phytochemical screening showed the presence of carbohydrates, saponins, tannins, phenols, quinines, proteins, terpenes, glycosides, and alkaloids. FTIR analysis revealed the existence of different functional groups in both extracts. The DPPH method showed that E. prostrata exhibited a high antioxidant potential with an IC50 of 62.5 µg/ml whereas C. burhia showed a lower antioxidant potential. At the dose of 200 mg/kg body weight (b. wt), both the extracts showed a significant increase in the phagocytic index by 5.2 ± 0.2, and, 4.8 ± 0.1 (p < 0.001) respectively which was close to the 100 mg/kg b. wt of the standard drug (Levamisole) 5.4 ± 0.2. Both the extracts at the dose of 200 mg/kg b. wt also significantly reduced the writhing (abdominal contractions) count by 13.7 ± 0.3 and, 25.3 ± 1.5 (p < 0.001), showing 71.8% and 47.6% of reduced analgesic activity compared to the standard drug dicloran (diclofenac sodium), respectively. In conclusion, extracts of both plants indicate their role in the management of various disorders to relieve pain and modulate the immune system.

16.
J Nutr Sci Vitaminol (Tokyo) ; 69(3): 184-189, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37394423

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that mediates many redox reactions in energy metabolism. NAD+ is also a substrate for ADP-ribosylation and deacetylation by poly (ADP-ribose) polymerase and sirtuin, respectively. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) is a NAD+ biosynthesizing enzyme found in the nucleus. Recent research has shown that the maintaining NAD+ levels is critical for sustaining muscle functions both in physiological and pathological conditions. However, the role of Nmnat1 in skeletal muscle remains unexplored. In this study, we generated skeletal muscle-specific Nmnat1 knockout (M-Nmnat1 KO) mice and investigated its role in skeletal muscle. We found that NAD+ levels were significantly lower in the skeletal muscle of M-Nmnat1 KO mice than in control mice. M-Nmnat1 KO mice, in contrast, had similar body weight and normal muscle histology. Furthermore, the distribution of muscle fiber size and gene expressions of muscle fiber type gene expression were comparable in M-Nmnat1 KO and control mice. Finally, we investigated the role of Nmnat1 in muscle regeneration using cardiotoxin-induced muscle injury model, but muscle regeneration appeared almost normal in M-Nmnat1 KO mice. These findings imply that Nmnat1 has a redundancy in the pathophysiology of skeletal muscle.


Assuntos
NAD , Nicotinamida-Nucleotídeo Adenililtransferase , Camundongos , Animais , NAD/metabolismo , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Camundongos Knockout , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo
17.
Diabetol Int ; 14(2): 125-133, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37090127

RESUMO

Adipose tissue-resident macrophages (ATMs) are reported to be important for maintaining adipose tissue remodeling and homeostasis. ATMs were classified for the first time in 2007 into the M1 and M2 types. This theory suggests that in the non-obese adipose tissue, the anti-inflammatory, alternatively activated macrophages (AAMs) predominate, and regulate tissue homeostasis, remodeling, and insulin sensitivity. On the other hand, classically activated M1-type macrophages increase rapidly in obesity, secrete inflammatory cytokines, such as TNFα and IL-6, and induce insulin resistance. In recent years, experimental findings that cannot be explained by this theory have been clarified one after another and the theory is being reconsidered. In this review, based on recent findings, we summarize reports on the novel metabolic regulatory functions of ATMs beyond the M1/M2 paradigm.

18.
Front Pharmacol ; 14: 1334160, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38283838

RESUMO

Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.

19.
Front Plant Sci ; 14: 1325370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38348163

RESUMO

Zinc (Zn) is essential for plants and animals as it plays significant roles in several physiological and biological processes. Its deficiency in soil results in low Zn content food and is one of the major reasons for Zn malnutrition in humans. Biofortification of crops with zinc (Zn) is a viable approach to combat malnutrition, especially in developing countries. A hydroponic study was executed to study response and Zn partitioning in various lentil genotypes. Eight preselected lentil genotypes (Line-11504, Mansehra-89, Masoor-2006, Masoor-85, Line-10502, Markaz-09, Masoor-2004, and Shiraz-96) were grown in solution culture with two Zn levels (control and adequate Zn). Plants were sown in polythene lined iron trays with a two inch layer of prewashed riverbed sand. After 10 days of germination, seedlings were transplanted to a 25L capacity container with nutrient solution for 15 days, and afterward, these plants were divided into two groups, receiving either 2.0 mM Zn or no Zn levels. Three plants of each genotype were harvested at the vegetative growth stage (60 DAT) and the remaining three at physiological maturity (117 DAT). Plants were partitioned into roots, shoots, and grains at harvest. Significant variations in root and shoot dry matter production, grain output, partitioning of Zn in plant parts (root, shoot, and grain), grain phytate reduction, and Zn bioavailability were observed among genotypes. Lentil root accumulated more Zn (54 mg kg-1) with respect to shoot Zn (51 mg kg-1) under Zn supply. The Zn efficient genotypes (Line-11504 and Mansehra-89) produced more root and shoot dry weights at both harvests. There was a positive correlation between the relative growth rate of root and grain phytate concentration (r = 0.55) and [phytate]:[Zn] ratio (r = 0.67). Zn-efficient genotype Mansehra-89 had a maximum root shoot ratio (0.57) and higher grain Zn (60 mg kg-1) with a respectively reduced grain phytate (17 µg g-1) and thus, had more Zn bioavailability (3.01 mg d-1). The genotypic ability for Zn uptake and accumulation within different plant tissues may be incorporated into future crop breeding to improve the nutrition of undernourished consumers.

20.
Mol Metab ; 77: 101797, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37709134

RESUMO

OBJECTIVE: Polyphenols have health-promoting effects, such as improving insulin resistance. Isoxanthohumol (IX), a prenylated flavonoid found in beer hops, has been suggested to reduce obesity and insulin resistance; however, the mechanism remains unknown. METHODS: High-fat diet-fed mice were administered IX. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice. RESULTS: The administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration increased markers of intestinal barrier function, including thickening the mucin layer and increasing caludin-1, a tight-junction related protein in the colon. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of Akkermansia muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A. muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A. muciniphila on lipid and glucose metabolism, we monocolonized either A. muciniphila or Bacteroides thetaiotaomicron to GF mice. A. muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis. CONCLUSIONS: Our study demonstrated that IX prevents obesity and enhances glucose metabolism by inhibiting dietary fat absorption. This mechanism is linked to suppressing pancreatic lipase activity and shifts in microbial composition, notably an increase in A. muciniphila. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.


Assuntos
Resistência à Insulina , Animais , Camundongos , RNA Ribossômico 16S/genética , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Verrucomicrobia/genética , Verrucomicrobia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta , Glucose/metabolismo , Lipase
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