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• Organic acids are acid in nature. • Dietary organic acids have no risk factors. • Organic acids have antimicrobial activity. • They attenuate Alzheimer disease via antioxidant activity to affect the amyloid aggregation pathway. Organic acids are specific groups of chemicals that contain COOH in their structures. They have properties of weakly acidic nature and dissolves completely into protons when present in aqueous solutions. In biological systems, organic acids are involved in various activities such as important intermediates in various metabolic cycles, antimicrobial compounds, and prediction of maturity indices. Due to these properties, organic acids are important phytochemicals that have a wide range of commercial applications like animal feeds utilization, improve plant quality, bactericidal and bacteriostatic potential, as well as in the pharmaceutical industry for numerous preparations. In pharmacokinetics, organic acids are primarily involved in the absorption of pH-dependent drugs. Different techniques have been employed for the extraction, purification, and quantification of organic acids. Among them, microwave-assisted extractions (MAE) and ultrasound-assisted extractions (UAE) are the chiefly used techniques where MAE is one of the most valuable methods for isolating different compounds from plant materials for industrial and analytical purposes. Moreover, bioactive chemicals such as natural organic acid from plants and other sources are important and referred as "lifespan essential"since they havea beneficial effect on healthy aging and Alzheimer's disease (AD). Therefore, dietary organic acids and avoiding risk factors, will reduce the risk of neurodegenerative diseases such as AD and increase a healthy lifespan. Thus, the present study aimed to understand the phytochemistry, biological activities, industrial applications, possible interaction with other drugs/foods supplements,techniques of extraction, purification and fractionation, techniques of identification and quantification, the effect of food processing,and molecular mechanisms of organic acid to attenuate AD. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disorder in which blood glucose level raises that can result in severe complications. However, the incidence increased mostly by obesity, pregnancy, persistent corpus luteum, and diestrus phase in humans and animals. This review has focused on addressing the possible understanding and pathogenesis of spontaneous DM in canine, feline, and few wild animals. Furthermore, pancreatic associated disorders, diabetic ketoacidosis, hormonal and drug interaction with diabetes, and herbal remedies associated with DM are elucidated. Bibliographic search for the present review was done using PubMed, Scopus, and Google Scholar for articles on concurrent DM in small and wild animals. Persistent corpus luteal and pseudopregnancy in female dogs generate gestational DM (GDM). GDM can also be caused by extensive use of drugs/hormones such as glucocorticosteroids. Although many similarities are present between diabetic cats and diabetic humans which present islet amyloidosis, there was a progressive loss of β- and α-cells and the normal number of δ-cells. The most prominent similarity is the occurrence of islet amyloidosis in all cases of diabetic cat and over 90% of human non-insulin dependent DM Type-2. Acute pancreatic necrosis (APN) occurs due to predisposing factors such as insulin antagonism, insulin resistance, alteration in glucose tolerance, obesity, hyperadrenocorticism, and persistent usage of glucocorticoids, as these play a vital role in the progression of APN. To manage such conditions, it is important to deal with the etiological agent, risk factors, diagnosis of diabetes, and hormonal and drug interaction along with its termination with suitable therapy (herbal) protocols. It should be noted that the protocols used for the diagnosis and treatment of human DM are not appropriate for animals. Further investigations regarding diabetic conditions of pets and wild animals are required, which will benefit the health status of all animals health worldwide. [ABSTRACT FROM AUTHOR]

Styrene is an aromatic hydrocarbon compound present in the environment and have primary exposure through plastic industry. The current study was designed to evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose (FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in corn oil and administered at different doses (250, 500, 1000, 1500, 2000 mg/kg/day and control) to each rat, for 42 days. In treated groups, styrene significantly increased fasting blood glucose, plasma insulin (p < 0.001) and glucose tolerance. Glucose tolerance, insulin resistance and hyperglycemia were found to be the main consequences correlating gene expression of islet cells. Styrene caused a significant enhancement of oxidative stress markers (p < 0.001) and inflammatory cytokines in a dose and concentration-dependent manner in plasma (p < 0.001). Moreover, the activities of caspase-3 and −9 of the islet cells were significantly up-regulated by this compound at 1500 and 2000 mg/kg/day styrene administrated groups (p < 0.001). The relative fold change of GLUD1 was downregulated (p < 0.05) and upregulated at 1500 and 2000 mg/kg, respectively (p < 0.01). The relative fold changes of GLUT2 were down regulated at 250 and 1000 mg/kg and up regulated in 500, 1500 and 2000 mg/kg doses of styrene (p < 0.01). The expression level of GCK indicated a significant upregulation at 250 mg/kg and downregulation of relative fold changes in the remaining doses of styrene, except for no change at 2000 mg/kg of styrene for GCK. Targeting genes (GLUD1, GLUT2 and GCK) of the pancreatic islet cells in styrene exposed groups, disrupted gluconeogenesis, glycogenolysis pathways and insulin secretory functions. The present study illustrated that fasting blood glucose, insulin pathway, oxidative balance, inflammatory cytokines, cell viability and responsible genes of glucose metabolism are susceptible to styrene, which consequently lead to other abnormalities in various organs. [ABSTRACT FROM AUTHOR]

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer. [ABSTRACT FROM AUTHOR]

The article presents a study conducted by the authors related to the role of bacterium UD1023 on the uptake and bioaccumulation of heavy metals in plants. Topics discussed include slowdown of arsenic movement into the roots and to the edible portion of the plants by the UD1023, study on mobilization of iron and reduced uptake of arsenic and other noxious heavy metals, and remediation strategies such as microbial and phytoremediation.

Xylene is a cyclic hydrocarbon, and an environmental pollutant. It is also used in dyes, paints, polishes, medical technology and different industries as a solvent. Xylene easily vaporizes and divides by sunlight into other harmless chemicals. The aim of the present review is to collect the evidence of the xylene toxicity, related to non-cancerous health hazards, as well as to provide possible effective measurement to minimize its risk ratio. For current study a bibliographic search of more than 250 peer-reviewed papers in scientific data including PubMed, and Google Scholar about xylene was done. But approximately 130 peer-reviewed papers relevant to xylene were included (Figure 1). All scientific data was reviewed with key words of "xylene toxicity", "xylene toxic health effects", "environmental volatile organic compounds", "human exposure to xylene", "xylene poisoning in laboratory workers", "effects of xylene along with other hydrocarbons", "neurotoxicity of selected hydrocarbons", and "toxic effects of particular xylene isomers in animals". According to these studies, xylene is released into the atmosphere as fugitive emissions from petrochemical industries, fire, cigarette, from different vehicles. Short term exposure to mixed xylene or their individual isomers result in irritation of the nose, eyes and throat subsequently leading toward neurological, gastrointestinal and reproductive harmful effects. In addition long term exposure to xylene may cause hazardous effects on respiratory system, central nervous system, cardiovascular system, and renal system. The health concerns of xylene are well documented in animals and human. It is important to improve health policies, launch xylene related health and toxicity awareness campaigns, to get rid of its dangerous outcomes. Chronic diseases have become a threat to human globally, with special prominence in regions, where xylene is used with other chemicals (benzene, toluene etc.) especially in petroleum and rubber industry. The mechanism of toxicity and interactions with endocrine system should be followed up which is the main threat to human health. [ABSTRACT FROM AUTHOR]

Mastitis is аn inflammation оf thе mammary gland, caused by the invasion and duplication оf Escherichia coli (E. coli), Staphylococcus uberis (S. uberis) аnd Staphylococcus aureus (S. aureus) аnd а wide variety оf оthеr microorganisms thrоugh teat оr damaged nipple, decreasing potential milk production іn thе affected quarter оf mammary gland. Economic, animal productivity, international trade and animal welfare issues associated with mastitis play an important role in the agricultural industry. Therefore, worldwide dairy cattle breeding programmes are trying to breed cows wіth improved resistance tо mastitis. Mastitis can't be eliminated but can be reduced to a low level. It can be achieved by breeding strategies, reducing the exposure to pathogen and increasing the resistance to intramammary infection. Numerous therapeutic, prophylactic аnd management techniques аrе uѕеd аѕ control and reduce the mastitis. However, а widely proposed strategy marker assisted selection uѕіng candidate gene approach which іѕ based оn improving thе host genetics. One of them is cluster of differentiation 4 (CD4) gene, which is а glycoprotein located оn receptors оf immune cells. CD4 exhibit аn essential role іn a variety of inflammation related conditions іn mаnу species. Therefore, CD4 as a candidate gene for resistance to mastitis has received considerable attention. The review is based on a study of CD4 in association with improving resistance to mastitis and it may be helpful in formulating breeding programmes and marker assisted selection to lower the mastitis. [ABSTRACT FROM AUTHOR]

Objective(s): During type-1 diabetes treating by pancreatic islet transplantation, increasing oxidative stress and microbial contaminations are the main reasons of transplantation failure. In this study, we evaluated anti-apoptotic, antioxidant and antimicrobial potentials of phenolic compounds called ellagic acid (EA) and silybin on rat pancreatic islets. Materials and Methods: By doing MTT assay, effective concentrations of EA and silybin were determined as 1500 and 2100 μM, respectively. Then, ELISA methods, flow cytometry and MIC were done to investigate antioxidant, anti-apoptotic and antibacterial effects of those compounds, respectively. Results: Results of FITC Annexin-V and PI staining via flow cytometry, and also caspase-3 and -9 activities performed that EA has anti-apoptotic effects on pancreatic cells. Both compounds significantly diminished reactive oxygen species, and enhanced antioxidant power and insulin secretion. Furthermore, the minimum inhibitory concentration test indicated that these two have antibacterial effects on both Gram-positive and Gram-negative bacteria which usually contaminate the pancreatic islets. Conclusion: These findings support that use of EA and silybin can improve the function of islets which are used in transplantation, along with decreasing islets bacterial contamination. [ABSTRACT FROM AUTHOR]

Background Exposure to inorganic arsenic (iAs) is a major threat to the human health worldwide. The consumption of arsenic in drinking water and other food products is associated with the risk of development of type-2 diabetes mellitus (T2DM). The available experimental evidence indicates that epigenetic alterations may play an important role in the development of diseases that are linked with exposure to environmental toxicants. iAs seems to be associated with the epigenetic modifications such as alterations in DNA methylation, histone modifications, and micro RNA (miRNA) abundance. Objective This article reviewed epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes. Method Electronic databases such as PubMed, Scopus and Google scholar were searched for published literature from 1980 to 2017. Searched MESH terms were “Arsenic”, “Epigenetic mechanism”, “DNA methylation”, “Histone modifications” and “Diabetes”. Results There are various factors involved in the pathogenesis of T2DM but it is assumed that arsenic consumption causes the epigenetic alterations both at the gene-specific level and generalized genome level. Conclusion The research indicates that exposure from low to moderate concentrations of iAs is linked with the epigenetic effects. In addition, it is evident that, arsenic can change the components of the epigenome and hence induces diabetes through epigenetic mechanisms, such as alterations in glucose transport and/or metabolism and insulin expression/secretion. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a well-known heavy metal and causes various toxic effects. It is abundantly present in fish in the form of methyl mercury (MeHg). Also, various other forms of mercury can enter human body either from environment like inhalation or through dental amalgams. The present study was designed to assess MeHg induced toxicity in mouse plasma and pancreatic islets with respect to insulin secretion, oxidative balance, glucose tolerance, gene expression, caspases 3 and 9 activities. MeHg was dissolved in tap water and administered at doses 2.5, 5 and 10 mg/kg/day, for 4 weeks. In mice, MeHg significantly caused increase in plasma insulin as well as C-peptides. Glucose intolerance, insulin resistance and hyperglycemia are main consequences of our study that correlate with the gene expression changes of glucose homeostasis as well. MeHg caused increase lipid peroxidation in a dose-dependent manner in plasma as well as pancreatic islets. In addition, total thiol molecules and ferrous reducing antioxidant power in MeHg treated group was decreased in plasma as well as pancreatic islets. Caspases 3 and 9 activities of pancreatic islets were upregulated in MeHg exposed animals. Reactive oxygen species were extremely high in pancreatic islets of MeHg treated groups. MeHg disrupted gluconeogenesis/glycogenolysis pathways and insulin secretory functions of islets by targeting GDH, GLUT2 and GCK genes of pancreatic islets. In conclusion, the current study revealed that insulin pathways, oxidative balance and glucose metabolism encoded genetic makeup are susceptible to MeHg toxicity and the subsequent oxidative stress and alternations in gene expression could lead toward functional abnormalities in other organs. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer's pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis. [ABSTRACT FROM AUTHOR]

Despite advances in sepsis management, it remains a major intensive-care-unit (ICU) concern. From new prospective, positive effects of metformin, such as anti-oxidant and anti-inflammatory properties are considered potentially beneficial properties for management of septic patients. This article reviewed the potential ameliorative effects of metformin in sepsis-induced organ failure. Information were retrieved from PubMed, Scopus, Embase, and Google Scholar. Multi-organ damage, oxidative stress, inflammatory cytokine stimulation, and altered circulation are hallmarks of sepsis. Metformin exerts its effect via adenosine monophosphate-activated protein kinase (AMPK) activation. It improves sepsis-induced organ failure by inhibiting the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, preventing the activation of transcription factors related to inflammation, decreasing neutrophil accumulation/infiltration, and also maintaining mitochondrial membrane potential. Studies reported the safety of metformin therapeutic doses, with no evidence of lactic acidosis, in septic patients. [ABSTRACT FROM AUTHOR]

The current rate of population growth is so fast that, to feed this massive population, a 2-fold increase in land is required for the production of quality food. Improved dietary products such as milk and its products with antioxidant properties and functional foods of animal origin have been utilized to prevent chronic diseases. The designer milk contains low fat and less lactose, more protein, modified level of fatty acids, and desired amino acid profiles. The importance of milk and its products is due to the presence of protein, bioactive peptides, conjugated linoleic acid, omega-3 fatty acid, Vitamin D, selenium, and calcium. These constituents are present in milk product, play a key role in the physiological activities in human bodies, and act as anti-inflammatory, anti-tumor, antioxidant, hypocholesterolemic, immune boosting, and antimicrobial activities. Consumer awareness regarding benefits of designer foods such as milk and its products is almost non-existent worldwide and needs to be established to reach the benefits of designer food technologies in the near future. The main objective of this review was to collect data on the antioxidant properties of milk and its constituents which keep milk-derived products safe and preserved. [ABSTRACT FROM AUTHOR]

Salient evidence testifies the link between organophosphorus (OPs) exposure and the formation of free radical oxidants; and it is well accepted that free radicals are one of the basic concerns of senescence. To show the oxidative features of phosalone (PLN) as a key member of OPs, to induce senescence in rat embryonic fibroblast (REF) cells and to demonstrate the beneficial effects of the known antioxidant ellagic acid (EA) in diminishing the PLN-induced toxic effects, the levels of cell viability, oxidative stress markers, inflammatory cytokines, telomerase activity, and the expression of the genes related to senescence were investigated. Our results lend support to the hypothesis that PLN enhances the entire premature senescence parameters of REF cells. This accounts for the mechanistic approval of the role of OPs in induction of senescence in rat fibroblasts. Moreover, incorporation of EA diminished PLN toxicity mainly through suppression of p38 and p53 at gene and protein levels, and tempered the inflammation factors (TNF-α, IL-1β, IL-6 and NF-κB), which further affected cell division. Analysis of cell cycle showed that the percentage of G0/G1 arrest, in REF cells treated by EA was elevated as compared to control and PLN treated cells. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family. It has a fast-spreading potential worldwide, which leads to high mortality regardless of lows death rates. Now some vaccines or a specific drug are approved but not available for every country for disease prevention and/or treatment. Therefore, it is a high demand to identify the known drugs and test them as a possible therapeutic approach. In this critical situation, one or more of these drugs may represent the only option to treat or reduce the severity of the disease, until some specific drugs or vaccines will be developed and/or approved for everyone in this pandemic. In this updated review, the available repurpose immunotherapeutic treatment strategies are highlighted, elucidating the crosstalk between the immune system and SARS-CoV-2. Despite the reasonable data availability, the effectiveness and safety of these drugs against SARS-CoV-2 needs further studies and validations aiming for a better clinical outcome. • Effective and novel therapies against COVID-19 are urgently needed. • SARS-CoV-2 invade the immune and nervous system. • Cytokines could be promising therapeutic target for the SARS-CoV-2 severe cases therapy. [ABSTRACT FROM AUTHOR]