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New analogs of the PPAR pan agonist AL29-26 encompassed ligand (S)-7 showing potent activation of PPARα and -γ subtypes as a partial agonist. In vitro experiments and docking studies in the presence of PPAR antagonists were performed to help interpretation of biological data and investigate the main interactions at the binding sites. Further in vitro experiments showed that (S)-7 induced anti-steatotic effects and enhancement of the glucose uptake. This latter effect could be partially ascribed to a significant inhibition of the mitochondrial pyruvate carrier demonstrating that (S)-7 also acted through insulin-independent mechanisms. In vivo experiments showed that this compound reduced blood glucose and lipid levels in a diabetic mice model displaying no toxicity on bone, kidney, and liver. To our knowledge, this is the first example of dual PPARα/γ partial agonist showing these combined effects representing, therefore, the potential lead of new drugs for treatment of dyslipidemic type 2 diabetes.
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Hipoglucemiantes , PPAR alfa , PPAR gamma , Animales , PPAR alfa/agonistas , PPAR alfa/metabolismo , PPAR gamma/agonistas , PPAR gamma/metabolismo , Ratones , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/síntesis química , Humanos , Relación Estructura-Actividad , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Estructura Molecular , Relación Dosis-Respuesta a Droga , Transportadores de Ácidos Monocarboxílicos/antagonistas & inhibidores , Transportadores de Ácidos Monocarboxílicos/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Simulación del Acoplamiento Molecular , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismoRESUMEN
Polyphenols, as secondary metabolites ubiquitous in plant sources, have emerged as pivotal bioactive compounds with far-reaching implications for human health. Plant polyphenols exhibit direct or indirect associations with biomolecules capable of modulating diverse physiological pathways. Due to their inherent abundance and structural diversity, polyphenols have garnered substantial attention from both the scientific and clinical communities. The review begins by providing an in-depth analysis of the chemical intricacies of polyphenols, shedding light on their structural diversity and the implications of such diversity on their biological activities. Subsequently, an exploration of the dietary origins of polyphenols elucidates the natural plant-based sources that contribute to their global availability. The discussion extends to the bioavailability and metabolism of polyphenols within the human body, unraveling the complex journey from ingestion to systemic effects. A central focus of the review is dedicated to unravelling the antioxidant effects of polyphenols, highlighting their role in combating oxidative stress and associated health conditions. The comprehensive analysis encompasses their impact on diverse health concerns such as hypertension, allergies, aging, and chronic diseases like heart stroke and diabetes. Insights into the global beneficial effects of polyphenols further underscore their potential as preventive and therapeutic agents. This review article critically examines the multifaceted aspects of dietary polyphenols, encompassing their chemistry, dietary origins, bioavailability/metabolism dynamics, and profound antioxidant effects. The synthesis of information presented herein aims to provide a valuable resource for researchers, clinicians, and health enthusiasts, fostering a deeper understanding of the intricate relationship between polyphenols and human health.
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l-cysteine, a primary building block of mycothiol, plays an essential role in the defense mechanism of Mycobacterium tuberculosis (Mtb). However, it is unclear how Mtb regulates cysteine biosynthesis as no study has reported the cysteine regulatory complex (CRC) in Mtb. Serine acetyltransferase (SAT) and cysteine synthase (CS) interact to form CRC. Although MtCS has been characterized well, minimal information is available on MtSAT, which synthesizes, O-acetylserine (OAS), the precursor of cysteine. This study fills the gap and provides experimental evidence for the presence of MtCRC and a non-canonical multi-oligomeric MtSAT. We employed multiple analytical methods to characterize the oligomeric and kinetic properties of MtSAT and MtCRC. Results show that MtSAT, lacking >75 N-terminal amino acids exists in three different assembly states; trimer, hexamer, and dodecamer, compared to the single hexameric state of SAT of other bacteria. While hexamers display the highest catalytic turnover, the trimer is the least active. The predominance of trimers at low physiologically relevant concentrations suggests that MtSAT displays the lowest catalytic potential known. Further, the catalytic potential of MtSAT is also significantly reduced in CRC state, in contrast to enhanced activity of SAT in CRC of other organisms. Our study provides insights into multi-oligomeric MtSAT with reduced catalytic potential and demonstrates that both MtSAT and MtCS of Mycobacterium interact to form CRC, although with altered catalytic properties. We discuss our results in light of the altered biochemistry of the last step of canonical sulfate-dependent cysteine biosynthesis of Mycobacterium.
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Proteínas Bacterianas , Cisteína Sintasa , Cisteína , Mycobacterium tuberculosis , Serina O-Acetiltransferasa , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/genética , Serina O-Acetiltransferasa/metabolismo , Serina O-Acetiltransferasa/genética , Serina O-Acetiltransferasa/química , Cisteína/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Cisteína Sintasa/metabolismo , Cisteína Sintasa/genética , Multimerización de Proteína , CinéticaRESUMEN
Bacterial blight (BB) is a devastating disease of rice in the tropics of Indian sub-continent, where the presence of Xoo races with varying levels of genetic diversity and virulence renders disease management extremely challenging. In this context, marker-assisted improvement of plant resistance has been proven as one of the most promising approaches for the development of sustainable rice cultivars. The present study demonstrates the marker-assisted introgression of the three BB resistant genes (Xa21 + xa13 + xa5) into the background of HUR 917, a popular aromatic short grain (ASG) rice cultivar in India. The performance of the resulting improved products (near isogenic lines (NILs), HR 23-5-37-83-5, HR 23-5-37-121-10, HR 23-5-37-121-14, HR 23-65-6-191-13, HR 23-65-6-237-2, HR 23-65-6-258-10 and HR 23-65-6-258-21) establishes the utility of marker-assisted selection (MAS) approach for accelerated trait introgression in rice. The MAS-bred lines carrying three introgressed genes showed broad spectrum BB resistance (lesion length, LL of 1.06 ± 1.35 cm to 4.61 ± 0.87 cm). Besides, these improved lines showed the complete product profile of recurrent parent HUR 917 along with the enhanced level of durable BB resistance. The improved introgression lines with durable BB resistance would contribute to sustainable rice production in India, particularly in the Indo-Gangetic plane that has substantial acreage under HUR 917.
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A new series of analogues or derivatives of the previously reported PPARα/γ dual agonist LT175 allowed the identification of ligand 10, which was able to potently activate both PPARα and -γ subtypes as full and partial agonists, respectively. Docking studies were performed to provide a molecular explanation for this different behavior on the two different targets. In vivo experiments showed that this compound induced a significant reduction in blood glucose and lipid levels in an STZ-induced diabetic mouse model displaying no toxic effects on bone, kidney, and liver. By examining in depth the antihyperglycemic activity of 10, we found out that it produced a slight but significant inhibition of the mitochondrial pyruvate carrier, acting also through insulin-independent mechanisms. This is the first example of a PPARα/γ dual agonist reported to show this inhibitory effect representing, therefore, the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.
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Diabetes Mellitus Tipo 2 , PPAR alfa , Ratones , Animales , PPAR alfa/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Transportadores de Ácidos Monocarboxílicos , Agonistas de PPAR-gamma , PPAR gamma/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéuticoRESUMEN
Every industry need helps to modify its working style quickly with the improvement of existing technology. New developing technologies improve production speed, reduce industrial process costs, etc. Technical specialists carry out continuous research and development to increase efficiency. A significant advance in 4D printing over 3D Printing is its capacity to alter shape over time because external elements such as pressure, air, heat, water, etc., use controlled impact. 4D Printing has one "D" instead of 3D Printing, and the fourth aspect is time. Therefore, its capacity to alter shape over time is a significant advancement of 4D printing over 3D printing technologies. It is evident that 4D printing will be of tremendous value to manufacturers regarding features and advances in dentistry. Its applications cover medical modelling, surgical guides manufacture, prosthodontics, dentistry, orthodontics, implantology, and dentistry instruments. This paper is brief about 4D printing and its printing of smart materials through 4D printing. Process workflow and Bio-Oriented 4D printable smart materials for dentistry are presented diagrammatically. Further, the paper identifies and discusses the significant potential of 4D printing for dentistry. 4D printing is an innovative technology that uses the inputs from smart materials, and the 3D printed item becomes another structure via the impact of external energy sources such as temperature, light, or other environmental stimuli. The objective is to integrate technology and design to create self-assembly and programmable material technologies that better design, production, and performance.
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We report a comparative study of a single plasma and a colliding laser produced plasma, investigated using a Faraday cup. An enhancement in ion emission and stagnation is observed in colliding plasma plume compared to single plasma plume. We observed that fast ion generation in laser ablated plasma can be achieved at large laser intensity on to the target. As laser intensity increases ionic yield increases for both colliding and single plume and at a fixed laser intensity ionic yield decreases with increase in ambient pressure. The double peak structure is observed in the ion signal at large fluence where the peaks correspond to fast and slow species. A Faraday cup composed of nine collectors is used to measure the spatial/angular distribution of ion of expanding plasma plume. Ionic yield is found to be larger in the colliding plasma plume than the single plasma plume at all spatial/angular positions.
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Regular hospital visits can be expensive, particularly in rural areas, due to travel costs. In the era of the Covid-19 Pandemic, where physical interaction becomes risky, people prefer telemedicine. Fortunately, medical visits can be reduced when telemedicine services are used through video conferencing or other virtual technologies. Thus, telemedicine saves both the patient's and the health care provider time and the cost of the treatment. Furthermore, due to its fast and advantageous characteristics, it can streamline the workflow of hospitals and clinics. This disruptive technology would make it easier to monitor discharged patients and manage their recovery. As a result, it is sufficient to state that telemedicine can create a win-win situation. This paper aims to explore the significant capabilities, features with treatment workflow, and barriers to the adoption of telemedicine in Healthcare. The paper identifies seventeen significant applications of telemedicine in Healthcare. Telemedicine is described as a medical practitioner to diagnose and treat patients in a remote area. Using health apps for scheduled follow-up visits makes doctors and patients more effective and improves the probability of follow-up, reducing missing appointments and optimising patient outcomes. Patients should have an accurate medical history and show the doctor any prominent rashes, bruises, or other signs that need attention through the excellent quality audio-video system. Further, practitioners need file management and a payment gateway system. Telemedicine technologies allow patients and doctors both to review the treatment process. However, this technology supplements physical consultation and is in no way a substitute for a physical consultation. Today this technology is a safe choice for patients who cannot go to the doctor or sit at home, especially during a pandemic.
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Cysteine Synthase (CS), the enzyme that synthesizes cysteine, performs non-canonical regulatory roles by binding and modulating functions of disparate proteins. Beyond its role in catalysis and regulation in the cysteine biosynthesis pathway, it exerts its moonlighting effect by binding to few other proteins which possess a C-terminal "CS-binding motif", ending with a terminal ILE. Therefore, we hypothesized that CS might regulate many other disparate proteins with the "CS-binding motif". In this study, we developed an iterative sequence matching method for mapping moonlighting biochemistry of CS and validated our prediction by analytical and structural approaches. Using a minimal protein-peptide interaction system, we show that five previously unknown CS-binder proteins that participate in diverse metabolic processes interact with CS in a species-specific manner. Furthermore, results show that signatures of protein-protein interactions, including thermodynamic, competitive-inhibition, and structural features, highly match the known CS-Binder, serine acetyltransferase (SAT). Together, the results presented in this study allow us to map the extreme multifunctional space (EMS) of CS and reveal the biochemistry of moonlighting space, a subset of EMS. We believe that the integrated computational and experimental workflow developed here could be further modified and extended to study protein-specific moonlighting properties of multifunctional proteins.
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Biología Computacional/métodos , Cisteína Sintasa/química , Cisteína Sintasa/metabolismo , Azorhizobium/genética , Sitios de Unión , Cristalografía por Rayos X , Cisteína Sintasa/genética , Bases de Datos de Proteínas , Fluorescencia , Haemophilus influenzae/enzimología , Histonas/química , Histonas/metabolismo , Cinética , Modelos Moleculares , Planctomycetales/enzimología , Regiones Promotoras Genéticas , Conformación Proteica , Mapas de Interacción de Proteínas , Ribosomas/química , Ribosomas/metabolismo , Especificidad de la Especie , Factores de Transcripción/química , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Three-dimensional (3D) printing technologies are part of additive manufacturing processes and are used to manufacture a 3D physical model from a digital computer-aided design model as per the required shape and size. These technologies are now used for advanced radiology applications by providing all information through 3D physical model. It provides innovation in radiology for clinical applications, treatment planning, procedural simulation, medical and patient education. Radiological advancements have been made in diagnosis and communication through medical digital imaging techniques like computed tomography, magnetic resonance imaging. These images are converted into Digital Imaging and Communications in Medicine in Standard Triangulate Language file format, easily printable in 3D printing technologies. This 3D model provides in-depth information about pathologic and anatomic states. It is useful to create new opportunities related to patient care. This article discusses the potential of 3D printing technology in radiology. The steps involved in 3D printing for radiology are discussed diagrammatically, and finally identified 12 significant applications of 3D printing technology for radiology with a brief description. A radiologist can incorporate this technology to fulfil different challenges such as training, planning, guidelines, and better communications.
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Introduction:Vitamin D plays a protective role against COVID-19. Patients with deficiency of vitamin D are more prone to severe SARS-CoV-2 infections. It is known to enhance human ß-defensin 2 and antimicrobial peptide. Vitamin D can easily stabilise and manage immunological reactions against SARS-CoV-2. It can also suppress the cytokine storm by boosting the innate system. Material and methods: RT-PCR confirmed COVID-19 positive subjects were divided into two groups, one comprising asymptomatic subjects (Group 1) and the other one ICU admitted patients (Group 2). In both groups, various comorbidities such as obesity, diabetes mellitus, hypertension, cardiovascular disease, respiratory disease, renal disease and malignancy were taken into consideration. Vitamin D estimation was performed along with serum levels of interleukin-6 (IL-6) and ferritin using automated immunoassays on Siemens Advia Centaur XP. Results:On acknowledging the cut-off serum concentration level of vitamin D as < 30 ng/mL for establishing vitamin D deficiency the prevalence of vitamin D deficiency was 66.18% in Group 1 and 98.30% in Group 2. Diabetes mellitus, followed by hypertension was associated comorbidity in both groups. In total, 33 patients were found to be severely deficient (<10 ng/mL) in vitamin D, out of which 27 were critically ill and six asymptomatic. In both groups, diabetes mellitus, followed by hypertension were the highest comorbid associations. Fatality rate (discharge vs fatality) was 0% in Group 1 and 16.94% (10 patients died) in Group 2. Conclusion:To conclude, the present study addressed the significant relationship between vitamin D levels and clinical outcomes of COVID-19 patients. Vitamin D deficiency distinctly upswings the chance of disease severity as well as mortality after SARS-CoV-2 infection.
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Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and inâ vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.
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Amidas/farmacología , Ácidos Cumáricos/farmacología , Inhibidores Enzimáticos/farmacología , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Peroxirredoxinas/antagonistas & inhibidores , Amidas/síntesis química , Amidas/química , Animales , Compuestos de Bifenilo/antagonistas & inhibidores , Supervivencia Celular/efectos de los fármacos , Ácidos Cumáricos/síntesis química , Ácidos Cumáricos/química , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/metabolismo , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Hipolipemiantes/síntesis química , Hipolipemiantes/química , Masculino , Modelos Moleculares , Estructura Molecular , Peroxirredoxinas/metabolismo , Picratos/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Estreptozocina , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
BACKGROUND AND AIM: The current global challenge of COVID-19 pandemic has surpassed the provincial, radical, conceptual, spiritual, social, and pedagogical boundaries. Internet of Things (IoT) enabled healthcare system is useful for proper monitoring of COVID-19 patients, by employing an interconnected network. This technology helps to increase patient satisfaction and reduces readmission rate in the hospital. METHODS: Searched the databases of Google Scholar, PubMed, SCOPUS and ResearchGate using the keywords "Internet of things" or "IoT" and "COVID-19". Further inputs are also taken from blogs and relevant reports. RESULTS: IoT implementation impacts on reducing healthcare cost and improve treatment outcome of the infected patient. Therefore, this present study based research is attempted to explore, discuss, and highlight the overall applications of the well-proven IoT philosophy by offering a perspective roadmap to tackle the COVID-19 pandemic. Finally, twelve significant applications of IoT are identified and discussed. It has ultimately forced the researchers, academicians, and scientists to propose some productive solutions to overcome or confront this pandemic. CONCLUSIONS: IoT is helpful for an infected patient of COVID-19 to identify symptoms and provides better treatment rapidly. It is useful for patient, physician, surgeon and hospital management system.
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Betacoronavirus/patogenicidad , Infecciones por Coronavirus/prevención & control , Atención a la Salud/normas , Control de Infecciones/métodos , Internet de las Cosas/estadística & datos numéricos , Pandemias/prevención & control , Neumonía Viral/prevención & control , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Humanos , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND AND AIMS: During COVID-19 pandemic, researchers are using innovative technologies for fast-tracking the development to end this menace. Virtual Reality (VR) also offers an imperative role for fighting this pandemic, through audiovisual-based virtual communication. METHODS: A brief study on Virtual Reality and its applications for the COVID-19 pandemic is carried out by employing keywords as Virtual reality or VR and COVID-19 from the databases of SCOPUS, Google Scholar, PubMed, Web of science Academia and ResearchGate. RESULTS: VR is beneficial for remote sites for exploring telemedicine, planning, treatment, and controlling of the infections by providing proper awareness to the people regarding this disease. CONCLUSIONS: VR technology develops a platform to reduce the face to face interaction of doctors with the infected COVID-19 patients. Through live video streaming, it helps to improve surveillance systems on the ongoing situation.
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Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Telemedicina/tendencias , Realidad Virtual , COVID-19 , Infecciones por Coronavirus/prevención & control , Sistemas de Apoyo a Decisiones Clínicas , Encuestas de Atención de la Salud , Humanos , Pandemias/prevención & control , Educación del Paciente como Asunto , Neumonía Viral/prevención & control , Pautas de la Práctica en MedicinaRESUMEN
Surface roughness is used to quantitatively evaluate the surface topography of the workpiece subjected to mechanical processing. The optimal machining parameters are critical to getting designed surface roughness. The effects of cutting speed, feed rate, and depth of cut on the areal surface roughness of AZ31B Mg alloys were investigated via experiments combined with regression analysis. An orthogonal design was adopted to process the dry turning experiment of the front end face of the AZ31B bar. The areal surface roughness Sa and Sz of the end face were measured with an interferometer and analyzed through direct analysis and variance analysis (ANOVA). Then, an empirical model was established to predict the value of Sa through multiple regression analysis. Finally, a verification experiment was carried out to confirm the optimal combination of parameters for the minimum Sa and Sz, as well as the availability of the regression model for predicting Sa. The results show that both Sa and Sz of the machined end face reduce with the decrease in feed rate. The minimum of Sa and Sz reaches to 0.577 and 5.480 µm, respectively, with the cutting speed of 85 m/min, the feed rate of 0.05 mm/rev, and a depth of cut of 0.3 mm. The feed rate, depth of cut, and cutting speed contribute the greatest, the second and the smallest to Sa, respectively. The linear regression model can predict Sa of AZ31B machined with dry face turning, since the cutting speed, feed rate and depth of cut can explain 97.5% of the variation of Sa.