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Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM.
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Antibacterianos , Antiinflamatorios , Mastitis Bovina , Plantas Medicinales , Animales , Bovinos , Mastitis Bovina/microbiología , Mastitis Bovina/tratamiento farmacológico , Mastitis Bovina/prevención & control , Plantas Medicinales/química , Antiinflamatorios/farmacología , Femenino , Antibacterianos/farmacología , Humanos , Leche , Dieta/veterinaria , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media.
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Oryza , Contaminantes Químicos del Agua , Humanos , Oryza/química , Agua , Colorantes/química , Adsorción , Cinética , Contaminantes Químicos del Agua/análisis , Concentración de Iones de HidrógenoRESUMEN
Onosma bracteata Wall. is an important medicinal and immunity-enhancing herbs. This plant is commonly used in the preparation of traditional Ayurvedic drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the present study aimed to investigate the antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human osteosarcoma (MG-63) cells. Among all the fractions isolated from O. bracteata, ethyl acetate fraction (Obea) showed good antioxidant activity in superoxide radical scavenging assay and lipid peroxidation assay with an EC50 value of 95.12 and 80.67 µg/mL, respectively. Silica gel column chromatography of ethyl acetate (Obea) fraction of O. bracteata yielded a pure compound, which was characterized by NMR, FTIR, and HR-MS analysis and was identified as 1,2-benzene dicarboxylic acid, bis (2-methyl propyl) ester (BDCe fraction). BDCe fraction was evaluated for the antiproliferative potential against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung carcinoma A549 cell lines by MTT assay and exhibited GI50 values of 37.53 µM, 56.05 µM, and 47.12 µM, respectively. In MG-63 cells, the BDCe fraction increased the level of ROS and simultaneously decreased the mitochondria membrane potential (MMP) potential by arresting cells at the G0/G1 phase, suggesting the initiation of apoptosis. Western blotting analysis revealed the upregulation of p53, caspase3, and caspase9 while the expressions of p-NF-κB, p-Akt and Bcl-xl were decreased. RT-qPCR studies also showed upregulation in the expression of p53 and caspase3 and downregulation in the expression of CDK2, Bcl-2 and Cyclin E genes. Molecular docking analysis displayed the interaction between BDCe fraction with p53 (-151.13 kcal/mol) and CDK1 (-133.96 kcal/mol). The results of the present work suggest that the BDCe fraction has chemopreventive properties against osteosarcoma (MG-63) cells through the induction of cell cycle arrest and apoptosis via Akt/NF-κB/p53 pathways. This study contributes to the understanding of the utilization of BDCe fraction in osteosarcoma treatment.
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Neoplasias Óseas , Boraginaceae , Osteosarcoma , Apoptosis , Boraginaceae/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ésteres , Humanos , Simulación del Acoplamiento Molecular , FN-kappa B/metabolismo , Osteosarcoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.
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Terapia Molecular Dirigida , Medicina de Precisión , Neoplasias de la Próstata/terapia , Proteínas de Unión al ARN/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.
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Antiinflamatorios/farmacología , Catecoles/farmacología , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Dietilnitrosamina , Alcoholes Grasos/farmacología , Estrés Oxidativo/efectos de los fármacos , Zingiber officinale/metabolismo , Albúminas/química , Animales , Compuestos de Bifenilo , Depuradores de Radicales Libres , Radicales Libres , Glutatión/metabolismo , Peróxido de Hidrógeno , Técnicas In Vitro , Inflamación/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Mitocondrias/metabolismo , Picratos , RatasRESUMEN
Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
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Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Animales , Antivirales/administración & dosificación , Antivirales/inmunología , Camelus/virología , Quirópteros/virología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Arabia Saudita/epidemiología , Zoonosis Virales/epidemiología , Zoonosis Virales/inmunología , Zoonosis Virales/transmisiónRESUMEN
Synthetic genomics is a novel field of chemical biology where the chemically modified genetic alphabets have been considered in central dogma of life. Tweaking of chemical compositions of natural nucleotide bases could be developed as novel building blocks of DNA/RNA. The modified bases (dP, dZ, dS, and dB etc.) have been demonstrated to be adaptable for replication, transcription and follow Darwinism law of evolution. With advancement of chemical biology especially nucleotide chemistry, synthetic genetic codes have been discovered and Hachimoji nucleotides are the most important and significant one among them. These additional nucleotide bases can form orthogonal base-pairing, and also follow Darwinian evolution and other structural features. In the Hachimoji base pairing, synthetic building blocks are formed using eight modified nucleotide (DNA/RNA) letters (hence the name "Hachimoji"). Their structural conformations, like polyelectrolyte backbones and stereo-regular building blocks favor thermodynamic stability and confirm Schrodinger aperiodic crystal. From the structural genomics aspect, these synthetic bases could be incorporated into the central dogma of life. Researchers have shown Hachimoji building blocks were transcribed to its RNA counterpart as a functional fluorescent Hachimoji aptamer. Apart from several unnatural nucleotide base pairs maneuvered into its in vitro and in vivo applications, this review describes future perspective towards the development and therapeutic utilization of the genetic codes, a primary objective of synthetic and chemical biology.
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ADN , Medicina de Precisión , ADN/química , Emparejamiento Base , Nucleótidos/química , ARN/genética , ARN/químicaRESUMEN
AIMS: Physical exercise has been widely recognized for its positive effects on health and well-being. Recently, the impact of exercise on the nervous system has gained attention, with evidence indicating improvements in attention, memory, neurogenesis, and the release of "happiness hormones." One potential mediator of these benefits is Irisin, a myokine induced by exercise that can cross the blood-brain barrier, reduce neuroinflammation, and counteract neurodegeneration. The objective of this study is to conduct a systematic review of animal trials to summarize the neuroprotective effects of Irisin injection in mitigating neuroinflammation and neurodegeneration. MATERIALS AND METHODS: Two independent reviewers screened three databases (PubMed, Embase, and Google Scholar) in November 2022. Animal studies assessing the neuroprotective effects of Irisin in mitigating neuroinflammation or counteracting neurodegeneration were included. The methodological quality of the included studies was assessed using SYRCLE's Risk of Bias tool. KEY FINDINGS: Twelve studies met the inclusion criteria. Irisin injection in rodents significantly reduced neuroinflammation, cytokine cascades, and neurodegeneration. It also protected neurons from damage and apoptosis, reduced oxidative stress, blood-brain barrier disruption, and neurobehavioral deficits following disease or injury. Various mechanisms were suggested to be responsible for these neuroprotective effects. Most of the included studies presented a low risk of bias based on SYRCLE's Risk of Bias tool. Irisin injection demonstrated the potential to alleviate neuroinflammation and counteract neurodegeneration in rodent models through multiple pathways. However, further research is needed to fully understand its mechanism of action and its potential applications in clinical practice and drug discovery.
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Fibronectinas , Fármacos Neuroprotectores , Animales , Fibronectinas/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/metabolismo , Enfermedades Neuroinflamatorias , Ejercicio Físico/fisiología , Encéfalo/metabolismoRESUMEN
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.
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Enfermedad de Alzheimer , Alucinógenos , Humanos , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Dietilamida del Ácido Lisérgico/farmacología , Dietilamida del Ácido Lisérgico/uso terapéutico , Psilocibina/farmacología , Psilocibina/uso terapéutico , N,N-DimetiltriptaminaRESUMEN
Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble ß-amyloid peptide (Aß) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.
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Envejecimiento , Enfermedad de Alzheimer , Barrera Hematoencefálica , Humanos , Enfermedad de Alzheimer/metabolismo , Barrera Hematoencefálica/metabolismo , Envejecimiento/metabolismo , Envejecimiento/fisiología , Animales , Factores de RiesgoRESUMEN
Alzheimer's disease (AD) is a very common neurodegenerative disorder associated with memory loss and a progressive decline in cognitive activity. The two major pathophysiological factors responsible for AD are amyloid plaques (comprising amyloid-beta aggregates) and neurofibrillary tangles (consisting of hyperphosphorylated tau protein). Polyphenols, a class of naturally occurring compounds, are immensely beneficial for the treatment or management of various disorders and illnesses. Naturally occurring sources of polyphenols include plants and plant-based foods, such as fruits, herbs, tea, vegetables, coffee, red wine, and dark chocolate. Polyphenols have unique properties, such as being the major source of anti-oxidants and possessing anti-aging and anti-cancerous properties. Currently, dietary polyphenols have become a potential therapeutic approach for the management of AD, depending on various research findings. Dietary polyphenols can be an effective strategy to tackle multifactorial events that occur with AD. For instance, naturally occurring polyphenols have been reported to exhibit neuroprotection by modulating the Aß biogenesis pathway in AD. Many nanoformulations have been established to enhance the bioavailability of polyphenols, with nanonization being the most promising. This review comprehensively provides mechanistic insights into the neuroprotective potential of dietary polyphenols in treating AD. It also reviews the usability of dietary polyphenol as nanoformulation for AD treatment.
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Enfermedad de Alzheimer , Polifenoles , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/dietoterapia , Enfermedad de Alzheimer/metabolismo , Polifenoles/farmacología , Humanos , Animales , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Nanopartículas/química , Dieta , Péptidos beta-Amiloides/metabolismo , Disponibilidad BiológicaRESUMEN
Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, ß-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.
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Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-ß plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3ß, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.
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Enfermedad de Alzheimer , Resistencia a la Insulina , Humanos , Enfermedad de Alzheimer/patología , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Glucógeno Sintasa Quinasa 3 beta , Péptidos beta-Amiloides/metabolismo , Sistemas de Liberación de MedicamentosRESUMEN
The current study evaluates the cytotoxicity, mode of cell death and chemical analysis of selected beauty products and evaluation of the protective effect of Tamarix articulata (TA) extract against toxicity induced by beauty products in skin fibroblasts (Hs27). MTT and Crystal violet (CV) assays were used to determine the dose-dependent cytotoxic effects of beauty products against Hs27 fibroblasts. DNA fragmentation assay and annexin-V staining were conducted to determine the mode of cell killing induced by evaluated beauty products. Quantification of reactive oxygen species (ROS) and antioxidant enzyme levels were used to evaluate the oxidative stress. Chemical analysis and heavy metals were evaluated to determine beauty products. Pre-treatment with TA extract for different time points followed by time-dependent exposure with beauty products to assess the protective effect of TA extract in Hs27 cells was analyzed by MTT and CV assays. Owing to the presence of various harmful heavy metals such as arsenic (As), chromium (Cr), cadmium (Cd), nickel (Ni), and lead (Pb) in beauty products, our results revealed that all beauty products induce significant cytotoxicity over time (1, 4 h) in a dose-dependent (125, 250, 500 µg/mL) manner. DNA fragmentation assay, quantification of apoptosis by annexin-V staining, determination of ROS and antioxidant enzymes (CAT, GSH-Px and SOD) revealed that the induced cytotoxicity was caused by oxidative stress-mediated apoptosis. However, pre-incubation with a safe dose (50 µg/mL) of TA for different times (24, 48 h) followed by exposure to various doses (62.5, 125, 250, 500 µg/mL) of beauty products for different times (1, 4 h) revealed significant (*p≤0.05, **p≤0.01) protection against beauty product-mediated cytotoxicity. The effect was more pronounced for 1 h exposure to beauty products compared to 4 h. Our study demonstrates that the due to the presence of heavy metals in synthetic beauty products exhibit marked toxicity to skin fibroblasts due to oxidative stress-mediated apoptosis. However, the presence of abundant bioactive polyphenols with promising antiscavenging activity in TA extracts significantly nullifies cytotoxicity promoted by examined beauty products in skin fibroblasts (Hs27).
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Metales Pesados , Tamaricaceae , Humanos , Tamaricaceae/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Metales Pesados/análisis , Estrés Oxidativo , Apoptosis , Fibroblastos/metabolismo , Anexinas/metabolismo , Anexinas/farmacologíaRESUMEN
Physiological barrier function is very difficult to replicate in vitro. This situation leads to poor prediction of candidate drugs in the drug development process due to the lack of preclinical modelling for intestinal function. By using 3D bioprinting, we generated a colitis-like condition model that can evaluate the barrier function of albumin nanoencapsulated anti-inflammatory drugs. Histological characterization demonstrated the manifestation of the disease in 3D-bioprinted Caco-2 and HT-29 constructs. A comparison of proliferation rates in 2D monolayer and 3D-bioprinted models was also carried out. This model is compatible with currently available preclinical assays and can be implemented as an effective tool for efficacy and toxicity prediction in drug development.
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BACKGROUND: Hyperglycemia-induced oxidative stress accelerates the process of apoptosis in tissues. Dilleniaindica (DI) is a medicinal plant, and its fruit contains many therapeutic properties. The therapeutic activity of the Methanolic Fruit Extract (MFE) of DI in attenuating oxidative stress and apoptosis in the liver and kidney tissues of alloxan-induced diabetic mice was analyzed in the present study. METHODS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE was conducted. GLUT4 protein expression analysis and lipid peroxidation assays were conducted to check for MFE effect by administering in diabetic mice. An ultrastructural study was conducted for both the tissues. In apoptotic studies, the TUNEL assay and apoptotic protein expression analysis was conducted. RESULTS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE showed the presence of two crucial antioxidants, ascorbic acid, and naringenin. In GLUT-4 protein expression analysis, MFE suppresses hyperglycemia by upregulating GLUT4 protein expression. Lipid peroxidation assay showed a decrease in malondialdehyde (MDA) upon MFE administration in diabetic mice. An ultrastructural study was conducted, and MFE was found to restore cellular alterations in diabetic tissues. In apoptotic studies, the TUNEL assay shows that MFE treatment showed fewer apoptotic cells than the diabetic group. The study also observed decreased caspase 3 protein expression and increased Bcl-2 protein expression. CONCLUSIONS: Therefore, it is inferred from the study that MFE can exert a protective effect by suppressing hyperglycemia and modulating oxidative stress and apoptosis in alloxan-administered diabetic mice.
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Diabetes Mellitus Experimental , Dilleniaceae , Hiperglucemia , Ratones , Animales , Aloxano/farmacología , Aloxano/uso terapéutico , Dilleniaceae/metabolismo , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Antioxidantes/metabolismo , Estrés Oxidativo , ApoptosisRESUMEN
Combinational treatment is a promising strategy for better cancer treatment outcomes. Chrysin and luteolin have demonstrated effective anticancer activity. Cisplatin and topotecan are commonly used for the treatment of human cancers. However, various side effects including drug resistance are an imperative restriction to use them as pharmacological therapy. Therefore, the aim was to use these agents in combination with flavones for better efficacy. In the present study, it was found that the combination of chrysin and cisplatin and luteolin and cisplatin significantly improved the anticancer effect as both the combinations showed synergistic interactions [combinational index (CI < 1)]. Remarkably, the combination of chrysin and luteolin with topotecan depicted the antagonistic interaction (CI > 1). Further, increased expression of the pro-apoptotic proteins Bax and caspase 8 and the inhibition of the antiapoptotic protein Bcl-2 were instituted in the synergistic doses (chrysin + cisplatin and luteolin + cisplatin), hence promoting apoptosis. Also, it was found that the synergistic combination inhibited the migration of HeLa cells by downregulation of metalloproteases and upregulation of TIMPs. However, there are no significant changes depicted in the antagonistic combinations which support their role in their antagonistic effects. Based on these results, it can be inferred that the two or more drug combinations need to be explored well for their interaction to enhance the therapeutic outcomes.
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Alzheimer's disease (AD) is characterized by the progressive degeneration of neuronal cells. With the increase in aged population, there is a prevalence of irreversible neurodegenerative changes, causing a significant mental, social, and economic burden globally. The factors contributing to AD are multidimensional, highly complex, and not completely understood. However, it is widely known that aging, neuroinflammation, and excessive production of reactive oxygen species (ROS), along with other free radicals, substantially contribute to oxidative stress and cell death, which are inextricably linked. While oxidative stress is undeniably important in AD, limiting free radicals and ROS levels is an intriguing and potential strategy for deferring the process of neurodegeneration and alleviating associated symptoms. Therapeutic compounds from natural sources have recently become increasingly accepted and have been effectively studied for AD treatment. These phytocompounds are widely available and a multitude of holistic therapeutic efficiencies for treating AD owing to their antioxidant, anti-inflammatory, and biological activities. Some of these compounds also function by stimulating cholinergic neurotransmission, facilitating the suppression of beta-site amyloid precursor protein-cleaving enzyme 1, α-synuclein, and monoamine oxidase proteins, and deterring the occurrence of AD. Additionally, various phenolic, flavonoid, and terpenoid phytocompounds have been extensively described as potential palliative agents for AD progression. Preclinical studies have shown their involvement in modulating the cellular redox balance and minimizing ROS formation, displaying them as antioxidant agents with neuroprotective abilities. This review emphasizes the mechanistic role of natural products in the treatment of AD and discusses the various pathological hypotheses proposed for AD.
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Enfermedad de Alzheimer , Antioxidantes , Humanos , Anciano , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Enfermedad de Alzheimer/patología , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Oxidación-ReducciónRESUMEN
Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.
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Terapia Genética , Trastornos Mentales , Humanos , Trastornos Mentales/genética , Trastornos Mentales/terapiaRESUMEN
This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels.