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1.
Heliyon ; 10(5): e26751, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38449596

RESUMEN

This study was conducted to observe the stock assessments of Tengara (Mystus tengara) in three different management systems of Baors (Oxbow lake) such as System-1, System-2, and System-3. In this study, 1806 specimens were sampled using traditional fishing nets to observe growth pattern, population structure, growth parameters, natural mortality (M), fishing mortality (F), total mortality (Z), recruitment pattern, exploitation rate (E), relative yield per-recruit (Y'/R), optimum catchable length, length at first capture, steady state biomass (SSB), and maximum sustainable yield (MSY) from January to December 2021. Digital slide calipers and a digital balance were used to measure each individual's total length (TL) and body weight (BW), respectively. An empirical maximum length-based model was used to calculate size at first sexual maturity (Lm), and optimum catchable length (Lopt) was calculated based on asymptotic length (L∞). The least square linear regression equation was used to determine the regression parameters. The value of regression parameter, 'b' was 3.01 for system-1, 2.78 for system-2, and 2.70 for system-3, indicating that growth pattern of Tengara is isometric in system-1, but negative allometric growth in system-2 and system-3. The highest asymptotic length (L∞) and weight (W∞) of Tengara were found in system-1 (11.19 cm and 13.67 g) in comparison with system-2, (10.98 cm and 12.49 g) and system-3 (9.09 cm and 6.96 g) respectively. The growth coefficient (K) of the von Bertalanffy growth function (VBGF) was 0.72 year-1, 0.72 year-1, and 0.73 year-1 for system-1, system-2 and system-3, respectively. The calculated M, F, Z were 1.72, 1.28, and 3.00 year-1 for system-1, 1.11, 0.67 and 1.78 year-1 for system-2 and 1.12, 0.84 and 1.96 year-1 for system-3 respectively. The calculated life span (tmax) was found 4.19 years for system-1, 4.15 years for system-2 and 4.12 years for system-3. The recruitment patterns showed that the highest relative percentage of recruits were found in July, June and September for system-1, system-2 and system-3 respectively, with the major recruitment peak occurring from April to June for system-1, May to June for system-2 and June to July for system-3. One minor recruitment peak also occurred from August to September in system-1. The exploitation rate was more or less same in all three systems indicating that Tengara is under exploited from all the Baors. The significantly highest SSB and MSY were found in system-1 (22.65 and 12.11 metric tons), compared to system-2 (16.16 and 10.28 metric tons) and system-3 (5.55 and 5.49 metric tons), respectively. Considering the values of regression parameters, recruitment pattern, SSB and MSY, system-1 was found more suitable for Tengara compared to system-2 and system-3 management practices of Baors. Finally, these findings will turn out to be paradigm for the impregnable management of Tengara in Baors of southwest Bangladesh.

2.
Biomed Pharmacother ; 174: 116497, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552443

RESUMEN

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field.


Asunto(s)
Antioxidantes , Apoptosis , Autofagia , Neoplasias , Fitoquímicos , Humanos , Autofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Antioxidantes/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología
3.
Chem Biodivers ; 21(3): e202301661, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38359057

RESUMEN

Both diabetes and cancer pose significant threats to public health. To overcome these challenges, nanobiotechnology offers innovative solutions for the treatment of these diseases. However, the synthesis of nanoparticles can be complex, costly and environmentally toxic. Therefore, in this study, we successfully synthesized Camellia sinensis silver nanoparticles (CS-AgNPs) biologically from methanolic leaf extract of C. sinensis and as confirmed by the visual appearance which exhibited strong absorption at 456 nm in UV-visible spectroscopy. The fourier transform infrared spectroscopy (FTIR) analysis revealed that phytochemicals of C. sinensis were coated with AgNPs. Scanning electron microscopy (SEM) analysis showed the spherical shape of CS-AgNPs, with a size of 15.954 nm, while X-ray diffraction spectrometry (XRD) analysis detected a size of 20.32 nm. Thermogravimetric analysis (TGA) indicated the thermal stability of CS-AgNPs. The synthesized CS-AgNPs significantly inhibited the ehrlich ascites carcinoma (EAC) cell growth with 53.42±1.101 %. The EAC cell line induced mice exhibited increased level of the serum aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), however this elevated serum parameter significantly reduced and controlled by the treatment with CS-AgNPs. Moreover, in a streptozotocin-induced diabetic mice model, CS-AgNPs greatly reduced blood glucose, total cholesterol, triglyceride, low-density lipoprotein (LDL) and creatinine levels. These findings highlight that the synthesized CS-AgNPs have significant anticancer and antidiabetic activities that could be used as promising particles for the treatment of these major diseases. However, pre-clinical and clinical trial should be addressed before use this particles as therapeutics agents.


Asunto(s)
Camellia sinensis , Diabetes Mellitus Experimental , Nanopartículas del Metal , Neoplasias , Ratones , Animales , Nanopartículas del Metal/química , Plata/química , Camellia sinensis/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Extractos Vegetales/química , Espectroscopía Infrarroja por Transformada de Fourier , Antibacterianos , Difracción de Rayos X
4.
Environ Monit Assess ; 196(2): 219, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291263

RESUMEN

The study conducted an investigation into the reproductive biology of M. pancalus and assessed the influence of water quality parameters and environmental factors on the spawning pattern within the Gajner Beel ecosystem in Bangladesh. A total of 1218 individuals of M. pancalus (46.39% males and 53.61% females) were collected monthly from the Gajner Beel during January to December 2018 using various fishing gears. The total length (TL) of each individual was measured using digital slide calipers, and the whole body weight (BW) was measured using an electronic balance. Fulton's conditions factor (KF) showed significant differences between males and females. The calculated Lm were 11.11 cm, 11.30 cm, and 11.10 cm based on maximum length, gonadosomatic index (GSI), and the logistic model. The spawning season extended from May through August, with June and July being peak months. The average total fecundity was 1495.52 ± 840.24, with a range of 370 to 4069. During peak spawning season, the average temperature and rainfall were 27°C and 370 mm, respectively. Rainfall, dissolved oxygen, total alkalinity, and pH all had a significant (p < 0.01) positive effect whereas temperature and TDS all had a significant (p > 0.01) negative effect on GSI. Annual air temperature in the study area increased by 0.053 °C/year, with a regression coefficient value (r2 = 0.1695), while annual mean rainfall decreased by 5.97mm/year (r2 = 0.076). This research will contribute to the development of conservation and management approaches of Mastacembelidae fish in relation to current climate variability in sub-tropical waters.


Asunto(s)
Ecosistema , Humedales , Animales , Femenino , Masculino , Calidad del Agua , Monitoreo del Ambiente , Reproducción , Estaciones del Año , Peces
5.
RSC Med Chem ; 14(12): 2768-2781, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38107179

RESUMEN

Malaria is still a complex and lethal parasitic infectious disease, despite the availability of effective antimalarial drugs. Resistance of malaria parasites to current treatments necessitates new antimalarials targeting P. falciparum proteins. The present study reported the design and synthesis of a series of a 2-(4-substituted piperazin-1-yl)-N-(5-((naphthalen-2-yloxy)methyl)-1,3,4-thiadiazol-2-yl)acetamide hybrids for the inhibition of Plasmodium falciparum dihydrofolate reductase (PfDHFR) using computational biology tools followed by chemical synthesis, structural characterization, and functional analysis. The synthesized compounds were evaluated for their in vitro antimalarial activity against CQ-sensitive PfNF54 and CQ-resistant PfW2 strain. Compounds T5 and T6 are the most active compounds having anti-plasmodial activity against PfNF54 with IC50 values of 0.94 and 3.46 µM respectively. Compound T8 is the most active against the PfW2 strain having an IC50 of 3.91 µM. Further, these active hybrids (T5, T6, and T8) were also evaluated for enzyme inhibition assay against PfDHFR. All the tested compounds were non-toxic against the Hek293 cell line with good selectivity indices. Hemolysis assay also showed non-toxicity of these compounds on normal uninfected human RBCs. In silico molecular docking studies were carried out in the binding pocket of both the wild-type and quadruple mutant Pf-DHFR-TS to gain further insights into probable modes of action of active compounds. ADME prediction and physiochemical properties support their drug-likeness. Additionally, they were screened for antileishmanial activity against L. donovani promastigotes to explore broader applications. Thus, this study provides molecular frameworks for developing potent antimalarials and antileishmanial agents.

6.
Mar Environ Res ; 192: 106222, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37852122

RESUMEN

Meretrix lyrata which is under the family of Veneridae and under the order of Venerida, is a nutritionally and economically important edible mussel in Bangladesh. However, studies on species identification and nutritional value in M. lyrata are scarce. Therefore, a detailed investigation was conducted on (i) species identification of the common edible mussel through DNA-barcoding and morphometrics, (ii) reproductive features, such as size at sexual maturity, spawning, and peak-spawning seasons under different environmental factors, and (iii) nutritional status through proximate analysis of M. lyrata mussel collected from the Bay of Bengal, Bangladesh. The results indicated that the size at sexual maturity for M. lyrata was 4.2 cm and the spawning seasons were significantly affected by the dissolve oxygen and salinity. The study also demonstrated that the spawning of M. lyrata occurred from January to June and December while peak spawning season was May in the Bay of Bengal. The higher protein and moisture contents with lower fat in M. lyrata indicated that are value-added seafood with higher nutritional values for consumers.


Asunto(s)
Bahías , Bivalvos , Animales , Mariscos , Alimentos Marinos , Reproducción , Valor Nutritivo , Estaciones del Año , Biología
7.
Int J Surg Case Rep ; 111: 108814, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37741078

RESUMEN

INTRODUCTION AND IMPORTANCE: Traumatic subluxation of C2-C3 with Atlanto-Axial dislocation is very rare and uncommon condition. Only a very few case reported. What constitutes appropriate management in cases of traumatic C2-C3 subluxation with Atlato-axial dislocation is still controversial due to the infrequency of this injury. We managed a patient who had traumatic C2-C3 subluxation with Atlanto-axial dislocation following a history of trauma through posterior approach successfully. CASE DESCRIPTION: A 45-year male day laborer presented with neck pain with progressive neurological deficit after two episodes of fall with heavy object within 1 year. Imaging revealed complete dislocation of C2 over C3 with Atlanto-Axial Dislocation. The patient was approached for posterior fixation with attempt to reduction per-operatively with skeletal traction and C1, C2, C3 joint distraction. After distraction of the joint, we achieved to do reduction of the C2-C3 and Atlanto-Axial joint. We did C1 lateral mass, C2 pedical and C3, C4 lateral mass screw and put a spacer in between C1-C2 facet joint. The patient was improved immediately after the operation. One year follow up shows, he was completely well. One year follow up shows in radiography proper alignment with fusion between C1, C2 and C3. CLINICAL DISCUSSION: Traumatic subluxation of the C2 vertebra is due to fractures of the lamina, articular facets, pedicles, or pars interarticularis and was first described by Bouvier in1843. To the best of our knowledge there has been 3/4 cases reported till now with traumatic C2-C3 subluxation with AAD. In three similar cases before ours, one was reported to be reduced after 3 weeks of bidirectional cervical traction and another two cases were managed by open reduction and stabilization. We managed this rare case surgically successfully through posterior approach with good outcome. CONCLUSION: Our management through posterior approach between C1 to C4 shows very good outcome with proper fusion. But it needs proper understanding the anatomy and mechanism of reduction by careful reading the image. Its needs more case description and management to establish a standard treatment for this type of disease.

8.
Eur J Med Chem ; 258: 115564, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37321109

RESUMEN

Malaria is a widespread infectious disease, causing nearly 247 million cases in 2021. The absence of a broadly effective vaccine and rapidly decreasing effectiveness of most of the currently used antimalarials are the major challenges to malaria eradication efforts. To design and develop novel antimalarials, we synthesized a series of 4,7-dichloroquinoline and methyltriazolopyrimidine analogues using a multi-component Petasis reaction. The synthesized molecules (11-31) were screened for in-vitro antimalarial activity against drug-sensitive and drug-resistant strains of Plasmodium falciparum with an IC50 value of 0.53 µM. The selected compounds were screened to evaluate in-vitro and in-silico enzyme inhibition efficacy against two cysteine proteases, PfFP2 and PfFP3. The compounds 15 and 17 inhibited PfFP2 with an IC50 = 3.5 and 4.8 µM, respectively and PfFP3 with an IC50 = 4.9 and 4.7 µM, respectively. Compounds 15 and 17 were found equipotent against the Pf3D7 strain with an IC50 value of 0.74 µM, whereas both were displayed IC50 values of 1.05 µM and 1.24 µM for the PfW2 strain, respectively. Investigation of effect of compounds on parasite development demonstrated that compounds were able to arrest the growth of the parasites at trophozoite stage. The selected compounds were screened for in-vitro cytotoxicity against mammalian lines and human red-blood-cell (RBC), which demonstrated no significant cytotoxicity associated with the molecules. In addition, in silico ADME prediction and physiochemical properties supported the drug-likeness of the synthesized molecules. Thus, the results highlighted the diphenylmethylpiperazine group cast on 4,7-dichloroquinoline and methyltriazolopyrimidine using Petasis reaction may serve as models for the development of new antimalarial agents.


Asunto(s)
Antimaláricos , Proteasas de Cisteína , Malaria , Animales , Humanos , Antimaláricos/química , Malaria/tratamiento farmacológico , Plasmodium falciparum , Eritrocitos , Mamíferos
9.
Heliyon ; 9(4): e14944, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37101637

RESUMEN

The current study is focused on a comprehensive stock assessment of Gudusia chapra to assess the stock status along with feeding habits, essential minerals content and risk to human health from exposure to heavy metals. A total of 723 specimens from the Bukvora Baor, Bangladesh were used to estimate the total body length (TL) and body weight (W) which ranged from 5.5 to 14.5 cm and 1.62-26.45 g, respectively. The estimated asymptotic length (L ∞) of this species (15.38) was in comparison with average length at 10 cm from 723 specimens along with the rate of 0.70 yr-1 for approaching to asymptotic length. The obtained growth performance index (φ) 2.2 indicates that this species is not economically feasible to bring under aquaculture. At an average annual water surface temperature of 28 °C, natural mortality, 1.71yr-1 indicating good ecological suitability of Bukvora oxbow lake (Baor). The estimated current exploitation ratio (0.24) reflected under-exploitation status with total instantaneous mortality (2.25 years-1) and fishing mortality (0.55 years-1). The recruitment pattern of this species was observed across the year, with main peak occurring during the period of April to May. The estimated total steady state biomass (3.91 metric ton) and MSY (4.40 metric ton) based on length-structured virtual population analysis (VPA) length-structured virtual population analysis (VPA) through FiSAT II schedule indicating the sustainable production of this species. The obtained values of proximate compositions (% of protein, fat, Moisture, ash) showed no significant variations during different seasons throughout the year. The monthly measurements of GaSI showed significant alterations (p < 0.05). The value of essential minerals (Na and Ca) was recorded 9.18 mg and 245.19 mg per 100 g of fish flesh, respectively. Target hazard quotient and Cancer risk for all detected heavy metals were far below the recommended levels by United States Environmental Protection Agency. Therefore, the target fish species from oxbow lake is safe and have no human health risk. Therefore, the outcomes of this research would be very worthwhile in carrying out specific management for G. chapra in Baor ecosystems.

10.
Eur J Med Chem ; 254: 115354, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37043996

RESUMEN

Multi-target directed ligands (MTDLs) have recently attracted significant interest due to their exceptional effectiveness against multi-factorial Alzheimer's disease. The present work described the development of pyrazine-based MTDLs using multicomponent Petasis reaction for the dual inhibition of tau-aggregation and human acetylcholinesterase (hAChE). The molecular structure of synthesized ligands was validated by 1H & 13C NMR and mass spectrometry. The screened compounds were shown to have a strong inhibitory effect at 10 µM concentration against tau-oligomerization and hAChE, but only moderate inhibitory activity against Aß42. Among all the compounds, the half-maximal inhibitory concentration (IC50) for 21 and 24 against hAChE were 0.71 µM and 1.09 µM, respectively, while they displayed half-maximal effective concentrations (EC50) values of 2.21 µM and 2.71 µM for cellular tau-oligomerization, respectively. Additionally, an MTT experiment using tau-expressing SH-SY5Y neuroblastoma cells revealed that 21 was more neuroprotective than the FDA-approved medication donepezil. Furthermore, an MD simulation study was performed to investigate the dynamics and stability of AChE-21 and AChE-24 complexes in an aqueous environment. The MM-PBSA calculations were performed to evaluate the binding of 21 and 24 with AChE, and the relative binding energy was calculated as -870.578 and -875.697 kJ mol-1, respectively. As a result, the study offered insight into the design of new MTDLs and highlighted 21 as a potential roadblock to the development of anti-AD medications.


Asunto(s)
Enfermedad de Alzheimer , Neuroblastoma , Fármacos Neuroprotectores , Humanos , Inhibidores de la Colinesterasa/química , Relación Estructura-Actividad , Acetilcolinesterasa/metabolismo , Diseño de Fármacos , Neuroblastoma/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/química , Péptidos beta-Amiloides/metabolismo
11.
Sci Adv ; 9(11): eadg8776, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36921040

RESUMEN

The aldol reaction is among the most powerful and strategically important carbon-carbon bond-forming transformations in organic chemistry. The importance of the aldol reaction in constructing chiral building blocks for complex small-molecule synthesis has spurred continuous efforts toward the development of direct catalytic variants. The realization of a general catalytic aldol reaction with control over both the relative and absolute configurations of the newly formed stereogenic centers has been a longstanding goal in the field. Here, we report a decarboxylative aldol reaction that provides access to all four possible stereoisomers of the aldol product in one step from identical reactants. The mild reaction can be carried out on a large scale in an open flask, and generates CO2 as the only by-product. The method tolerates a broad substrate scope and generates chiral ß-hydroxy thioester products with substantial downstream utility.

12.
Cells ; 12(3)2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36766800

RESUMEN

Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via a lysosomal breakdown. This mechanism has been associated with the development of various pathologic conditions, including cancer and neurological disorders; however, recently updated studies have indicated that autophagy plays a dual role in cancer, acting as a cytoprotective or cytotoxic mechanism. Numerous preclinical and clinical investigations have shown that inhibiting autophagy enhances an anticancer medicine's effectiveness in various malignancies. Autophagy antagonists, including chloroquine and hydroxychloroquine, have previously been authorized in clinical trials, encouraging the development of medication-combination therapies targeting the autophagic processes for cancer. In this review, we provide an update on the recent research examining the anticancer efficacy of combining drugs that activate cytoprotective autophagy with autophagy inhibitors. Additionally, we highlight the difficulties and progress toward using cytoprotective autophagy targeting as a cancer treatment strategy. Importantly, we must enable the use of suitable autophagy inhibitors and coadministration delivery systems in conjunction with anticancer agents. Therefore, this review briefly summarizes the general molecular process behind autophagy and its bifunctional role that is important in cancer suppression and in encouraging tumor growth and resistance to chemotherapy and metastasis regulation. We then emphasize how autophagy and cancer cells interacting with one another is a promising therapeutic target in cancer treatment.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/patología , Cloroquina/farmacología , Cloroquina/uso terapéutico , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Autofagia
13.
Toxics ; 11(2)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36851010

RESUMEN

Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease's molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.

14.
Antioxidants (Basel) ; 12(2)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36829987

RESUMEN

Autophagy is a fundamental homeostatic process in which certain cellular components are ingested by double-membrane autophagosomes and then degraded to create energy or to maintain cellular homeostasis and survival. It is typically observed in nutrient-deprived cells as a survival mechanism. However, it has also been identified as a crucial process in maintaining cellular homeostasis and disease progression. Normal cellular metabolism produces reactive oxygen (ROS) and nitrogen species at low levels. However, increased production causes oxidative stress, which can lead to diabetes, cardiovascular diseases, neurological disorders, and cancer. It was recently shown that maintaining redox equilibrium via autophagy is critical for cellular responses to oxidative stress. However, little is understood about the molecular cancer processes that connect to the control of autophagy. In cancer cells, oncogenic mutations, carcinogens, and metabolic reprogramming cause increased ROS generation and oxidative stress. Recent studies have suggested that increased ROS generation activates survival pathways that promote cancer development and metastasis. Moreover, the relationship between metabolic programming and ROS in cancer cells is involved in redox homeostasis and the malignant phenotype. Currently, while the signaling events governing autophagy and how redox homeostasis affects signaling cascades are well understood, very little is known about molecular events related to autophagy. In this review, we focus on current knowledge about autophagy modulation and the role of redox metabolism to further the knowledge of oxidative stress and disease progression in cancer regulation. Therefore, this review focuses on understanding how oxidation/reduction events fine-tune autophagy to help understand how oxidative stress and autophagy govern cancer, either as processes leading to cell death or as survival strategies for maintaining redox homeostasis in cancer.

15.
Mol Divers ; 27(3): 1309-1322, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35821161

RESUMEN

Hepatitis C virus (HCV) infection is a major public health concern, and almost two million people are infected per year globally. This is occurred by the diverse spectrum of viral genotypes, which are directly associated with chronic liver disease (fibrosis, and cirrhosis). Indeed, the viral genome encodes three principal proteins as sequentially core, E1, and E2. Both E1 and E2 proteins play a crucial role in the attachment of the host system, but E2 plays a more fundamental role in attachment. The researchers have found the "E2-CD81 complex" at the entry site, and therefore, CD81 is the key receptor for HCV entrance in both humans, and chimpanzees. So, the researchers are trying to block the host CD81 receptor and halt the virus entry within the cellular system via plant-derived compounds. Perhaps that is why the current research protocol is designed to perform an in silico analysis of the flavonoid compounds for targeting the tetraspanin CD81 receptor of hepatocytes. To find out the best flavonoid compounds from our library, web-based tools (Swiss ADME, pKCSM), as well as computerized tools like the PyRx, PyMOL, BIOVIA Discovery Studio Visualizer, Ligplot+ V2.2, and YASARA were employed. For molecular docking studies, the flavonoid compounds docked with the targeted CD81 protein, and herein, the best-outperformed compounds are Taxifolin, Myricetin, Puerarin, Quercetin, and (-)-Epicatechin, and outstanding binding affinities are sequentially - 7.5, - 7.9, - 8.2, - 8.4, and - 8.5 kcal/mol, respectively. These compounds have possessed more interactions with the targeted protein. To validate the post docking data, we analyzed both 100 ns molecular dynamic simulation, and MM-PBSA via the YASARA simulator, and finally finds the more significant outcomes. It is concluded that in the future, these compounds may become one of the most important alternative antiviral agents in the fight against HCV infection. It is suggested that further in vivo, and in vitro research studies should be done to support the conclusions of this in silico research workflow.


Asunto(s)
Hepacivirus , Hepatitis C , Humanos , Hepacivirus/genética , Hepacivirus/metabolismo , Simulación del Acoplamiento Molecular , Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Hepatitis C/metabolismo , Hepatocitos/metabolismo , Flavonoides/farmacología , Flavonoides/metabolismo , Tetraspanina 28/genética , Tetraspanina 28/metabolismo , Tetraspanina 28/farmacología
16.
Mol Divers ; 27(2): 857-871, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35639226

RESUMEN

SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (MPRO or 3CLPRO) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4''''''-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the MPRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (MPRO). MPRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (- 8.9, - 9.4, - 9.7, - 9.1, - 9.3, - 9.0, - 9.7, - 9.3, - 8.8, and - 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4''''''-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Farmacología en Red , Inhibidores de Proteasas/química , Proteínas no Estructurales Virales , Antivirales/química , Péptido Hidrolasas/metabolismo
17.
Heliyon ; 8(11): e11326, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36339764

RESUMEN

The purpose of studying the consequence of COVID-19 on oxbow lake (Baor) fisher's community is to counteract the negative impacts on livelihoods with food security and figure out diversified resilience options for sustaining basic needs of life. Individual questionnaire interviews, oral history, focus group discussion, and telephonic interviews were among the methodological techniques used to gather primary data. The Baor fisher's community was impaired with income, food and feeding habit, health and marketing. The Baor fishers had to stop harvesting or reducing the amount of fish harvest because of gradual decreasing of consumer demand and prices of fish during the course of COVID-19 pandemic period. The transportation costs were raised up to 50%-80%, while the prices of fish decreased by 15%-30% prior to the onset of COVID-19 pandemic. The frequency of fish consumption was significantly come down to 37.5%. Many households substituted fish to farm reared hens, eggs, domestic hens and ducks, lentils, and vegetables during the period of lockdown across the country. Supply chains of fish and fish culture inputswere disrupted due to inadequacy of transportation facilities. Many school- and college-going students were dropped outduring the ongoing pandemic situation due to their financial problems (10%) and early marriage (7.5%). The secondary sources of income (labor of netting in other aquaculture farms) of Baor fisher's community were also impaired. The resilience options of this study will be helpful to minimize the sudden economic crises, ensure dynamic fish value chains and food security, protect individuals from ongoing health hazards, and promote sustainable food production systems followed by social cohesion and stabilityagainst the prevailing challenges owing to the pandemic and other natural calamities.

18.
Int J Mol Sci ; 23(19)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36233051

RESUMEN

Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.


Asunto(s)
Proteína HMGB1 , Neoplasias , Apoptosis , Proteína HMGB1/metabolismo , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quercetina/farmacología , Quercetina/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteína p53 Supresora de Tumor
19.
Eur J Med Chem ; 243: 114793, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36201858

RESUMEN

With an aim to develop novel potential antitumor agents, two series of benzene- and benzothiazole-sulfonamide derivatives, acting as effective human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors, have been developed using the tail approach. The synthesized compounds (XS-1 to XS-22) were assayed for the inhibition of physiologically relevant isoforms of hCA, the cytosolic CA I and II, the membrane-bound CA IV and tumor-associated CA IX. It was found the compounds of both series displayed low to medium nanomolar range inhibition against CA I, II and IX, and weak inhibition against CA IV. Some of the derivatives displayed selective inhibition towards tumor-associated CA IX isoform, within the nanomolar range. These potent compounds were also screened for their selective toxicity to evaluate their in vitro anti-proliferative effects on Human Gingival Fibroblasts (HGFs) and breast adenocarcinoma cell line (MCF7). Lastly, molecular docking studies were carried out to explain those structural requirements that were liable for the discrimination among selected human carbonic anhydrase isoforms.


Asunto(s)
Anhidrasas Carbónicas , Neoplasias , Humanos , Anhidrasa Carbónica IX/metabolismo , Anhidrasa Carbónica I/metabolismo , Inhibidores de Anhidrasa Carbónica/química , Benceno/farmacología , Anhidrasa Carbónica II/metabolismo , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Anhidrasas Carbónicas/metabolismo , Sulfonamidas/farmacología , Sulfonamidas/química , Neoplasias/tratamiento farmacológico , Benzotiazoles/farmacología , Isoformas de Proteínas/metabolismo
20.
Antioxidants (Basel) ; 11(10)2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36290765

RESUMEN

Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

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