Modification of the drug resistance of emerging milk-borne pathogens through sodium alginate-based antibiotics and nanoparticles.

Streptococcus agalactiae and Klebsiella pneumoniae are emerging as major milk-borne pathogens. Additionally, resistance to antibiotics of pathogens is of concern. Therefore, this study investigated the prevalence and drug resistance of S. agalactiae and K. pneumoniae in mastitis milk samples and assessed the antimicrobial potential of sodium alginate (G)-stabilized MgO nanoparticles (M) and antibiotics (tylosin [T] and ampicillin [A]) against both of these pathogens. A total of n = 200 milk samples from cattle were collected using purposive sampling, and standard microbiological approaches were adopted to isolate target bacteria. Parametric and non-parametric statistical tests were used to analyze the obtained data. Four preparations, GT (gel-stabilized tylosin), GA (gel-stabilized ampicillin), GTM (tylosin and MgO nanoparticles stabilized in gel), and GAM (ampicillin and MgO nanoparticles stabilized in gel), were evaluated against both bacteria through well diffusion and broth microdilution method. The analysis revealed that 45.24% (95/210) of the milk samples were positive for mastitis, of which 11.58% (11/95) were positive for S. agalactiae and 9.47% (9/95) were positive for K. pneumoniae. S. agalactiae had a significantly higher zone of inhibition (ZOI) than K. pneumoniae against penicillin, tetracycline, and amoxicillin, whereas the opposite was observed against imipenem and erythromycin. All gel (G)-based preparations showed an increase in the percentage of ZOI compared with antibiotics alone, with GTM presenting the highest of all, i.e., 59.09 and 56.25% ZOI compared with tylosin alone against S. agalactiae and K. pneumoniae, respectively. Similarly, in a broth microdilution assay, the lowest MIC was found for K. pneumoniae (9.766 ± 0.0 µg/mL) against GTM, followed by GT, GAM, and GA after incubation for 24 h. A similar response was noted for preparations against S. agalactiae but with a comparatively higher MIC. A significant reduction in MIC with respect to incubation time was found at 8 h and remained until at 20 h against both pathogens. The cytotoxicity of the MgO nanoparticles used in this study was significantly lower than that of the positive control. Overall, this study found that K. pneumoniae and S. agalactiae appeared higher in prevalence and antimicrobial resistance, and sodium alginate-based antibiotics and MgO nanoparticles were effective alternative approaches for tackling antimicrobial resistance.

Development of Iron Sequester Antioxidant Quercetin@ZnO Nanoparticles with Photoprotective Effects on UVA-Irradiated HaCaT Cells.

BACKGROUND: Solar ultraviolet radiation A (UVA, 320-400 nm) is a significant risk factor leading to various human skin conditions such as premature aging or photoaging. This condition is enhanced by UVA-mediated iron release from cellular iron proteins affecting huge populations across the globe. PURPOSE: Quercetin-loaded zinc oxide nanoparticles (quercetin@ZnO NPs) were prepared to examine its cellular iron sequestration ability to prevent the production of reactive oxygen species (ROS) and inflammatory responses in HaCaT cells. METHODS: Quercetin@ZnO NPs were synthesized through a homogenous precipitation method, and the functional groups were characterized by Fourier transform infrared (FTIR) spectroscopy, whereas scanning electron microscopy (SEM) described the morphologies of NPs. MTT and qRT-PCR assays were used to examine cell viability and the expression levels of various inflammatory cytokines. The cyclic voltammetry (CV) was employed to evaluate the redox potential of quercetin-Fe3+/quercetin-Fe2+ complexes. RESULTS: The material characterization results supported the loading of quercetin molecules on ZnO NPs. The CV and redox potential assays gave Fe-binding capability of quercetin at 0.15 mM and 0.3 mM of Fe(NO3)3. Cytotoxicity assays using quercetin@ZnO NPs with human HaCaT cells showed no cytotoxic effects and help regain cell viability loss following UVA (150 kJ/m2). CONCLUSION: Quercetin@ZnO NPs showed that efficient quercetin release action is UV-controlled, and the released quercetin molecules have excellent antioxidant, anti-inflammatory, and iron sequestration potential. Quercetin@ZnO NPs have superior biocompatibility to provide UVA protection and medication at once for antiphotoaging therapeutics.

Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review.

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.

Ochratoxin A-induced genotoxic and epigenetic mechanisms lead to Alzheimer disease: its modulation with strategies.

Ochratoxin A (OTA) is a naturally occurring mycotoxin mostly found in food items including grains and coffee beans. It induces DNA single-strand breaks and has been considered to be carcinogenic. It is recognized as a serious threat to reproductive health both in males and females. OTA is highly nephrotoxic and carcinogenic, and its potency changes evidently between species and sexes. There is a close association between OTA, mutagenicity, carcinogenicity, and genotoxicity, but the underlying mechanisms are not clear. Reports regarding genotoxic effects in relation to OTA which leads to the induction of DNA adduct formation, protein synthesis inhibition, perturbation of cellular energy production, initiation of oxidative stress, induction of apoptosis, influences on mitosis, induction of cell cycle arrest, and interference with cytokine pathways. All these mechanisms are associated with nephrotoxicity, hepatotoxicity, teratotoxicity, immunological toxicity, and neurotoxicity. OTA administration activates various mechanisms such as p38 MAPK, JNKs, and ERKs dysfunctions, BDNF disruption, TH overexpression, caspase-3 and 9 activation, and ERK-1/2 phosphorylation which ultimately lead to Alzheimer disease (AD) progression. The current review will focus on OTA in terms of recent discoveries in the field of molecular biology. The main aim is to investigate the underlying mechanisms of OTA in regard to genotoxicity and epigenetic modulations that lead to AD. Also, we will highlight the strategies for the purpose of attenuating the hazards posed by OTA exposure.

Circadian and sleep dysfunction in Alzheimer's disease.

Alzheimer's disease (AD) is a devastating and irreversible cognitive impairment and the most common type of dementia. Along with progressive cognitive impairment, dysfunction of the circadian rhythms also plays a pivotal role in the progression of AD. A mutual relationship among circadian rhythms, sleep, and AD has been well-recommended. The etiopathogenesis of the disturbances of the circadian system and AD share some general features that also unlock the outlook of observing them as a mutually dependent pathway. Indeed, the burden of amyloid ß (Aß), neurofibrillary tangles (NFTs), neuroinflammation, oxidative stress, and dysfunction of circadian rhythms may lead to AD. Aging can alter both sleep timings and quality that can be strongly disrupted in AD. Increased production of Aß and reduced Aß clearance are caused by a close interplay of Aß, sleep disturbance and raised wakefulness. Besides Aß, the impact of tau pathology is possibly noteworthy to the sleep deprivation found in AD. Hence, this review is focused on the primary mechanistic complexities linked to disruption of circadian rhythms, sleep deprivation, and AD. Furthermore, this review also highlights the potential therapeutic strategies to abate AD pathogenesis.

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer's Disease.

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 (Aß) 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 Aß peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aß 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.

A Review on The Protective Effects of Metformin in Sepsis-Induced Organ Failure.

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.

Magnitude and determinants of complementary feeding practices in Ethiopia: A systematic review and meta-analysis.

BACKGROUND & AIM: Concurrent estimates on the magnitude and evidence on the determinants of complementary feeding (CF) practices in Ethiopia are currently disparate. Hence, this systematic review and meta-analysis assessed the magnitude and determinants of CF among children age 6-23 months in Ethiopia. METHODS: Studies from various databases published until July 2018 were identified, selected, extracted and assessed for risk of bias by two authors independently. A random-effects model was used to pool the prevalence and odds ratios (ORs). RESULTS: 26 studies with 17, 383 children were included. The pooled prevalence estimate of timely initiated CF, minimum dietary diversity (DD), minimum meal frequency and minimum acceptable diet were 61.0%, 18.0%, 56.0%, and 10.0% respectively. The pooled prevalence of timely initiation and minimum DD were higher in Northern Ethiopia. On the other hand, except for the minimum meal frequency, all the three core indicators of CF were better in urban than rural settings. Child age, maternal and/or paternal education, paternal involvement, maternal DD, antenatal and postnatal care, and place of delivery were the main determinants that can increase appropriate CF practices. CONCLUSION: The reported estimates of the prevalence of core CF indicators in Ethiopia remained poor. Therefore, the authors would like to acknowledge the effort that has been done by the minister of health and its partners including Alive & Thrive to improving CF practices in the country, however, these programs should be done more thoroughly, and scaled up by applying and adapting tested, proven approaches and tools in contexts.

Endothelial PPARγ Is Crucial for Averting Age-Related Vascular Dysfunction by Stalling Oxidative Stress and ROCK.

Aging plays a significant role in the progression of vascular diseases and vascular dysfunction. Activation of the ADP-ribosylation factor 6 and small GTPases by inflammatory signals may cause vascular permeability and endothelial leakage. Pro-inflammatory molecules have a significant effect on smooth muscle cells (SMC). The migration and proliferation of SMC can be promoted by tumor necrosis factor alpha (TNF-α). TNF-α can also increase oxidative stress in SMCs, which has been identified to persuade DNA damage resulting in apoptosis and cellular senescence. Peroxisome proliferator-activated receptor (PPAR) acts as a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. They play key roles in a wide range of biological processes, including cell differentiation and proliferation, bone formation, cell metabolism, tissue remodeling, insulin sensitivity, and eicosanoid signaling. The PPARγ activation regulates inflammatory responses, which can exert protective effects in the vasculature. In addition, loss of function of PPARγ enhances cardiovascular events and atherosclerosis in the vascular endothelium. This appraisal, therefore, discusses the critical linkage of PPARγ in the inflammatory process and highlights a crucial defensive role for endothelial PPARγ in vascular dysfunction and disease, as well as therapy for vascular aging.

Biochemical evidence on the potential role of methyl mercury in hepatic glucose metabolism through inflammatory signaling and free radical pathways.

Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators' cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.

Correction to: Endothelial PPARγ Is Crucial for Averting Age-Related Vascular Dysfunction by Stalling Oxidative Stress and ROCK.

The original article unfortunately contains minor errors in Figs. 1 and 2. The correct Fig. 1 is shown below. The correct Fig. 2 is shown below.

The antioxidant components of milk and their role in processing, ripening, and storage: Functional food.

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.

Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease.

Quercetin belongs to the flavonoids family, which is present in most of the plants including fruits, vegetables, green tea and even in red wine having antioxidant activities. It is available as a food supplement in the market and has physiological health effects. Quercetin has anti-inflammatory, anticancer and anti-prostate activities along with its beneficial effects on high cholesterol, kidney transplantation, asthma, diabetes, viral infections, pulmonary, schizophrenia and cardiovascular diseases. Quercetin possesses scavenging potential of hydroxyl radical (OH-), hydrogen peroxide (H2O2), and superoxide anion (O2-). These reactive oxygen species (ROS) hampers lipid, protein, amino acids and deoxyribonucleic acid (DNA) processing leading to epigenetic alterations. Quercetin has the ability to combat these harmful effects. ROS plays a vital role in the progression of Alzheimer's disease (AD), and we propose that quercetin would be the best choice to overcome cellular and molecular signals in regulating normal physiological functions. However, data are not well documented regarding exact cellular mechanisms of quercetin. The neuroprotective effects of quercetin are mainly due to potential up- and/or down-regulation of cytokines via nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Paraoxonase-2, c-Jun N-terminal kinase (JNK), Protein kinase C, Mitogen-activated protein kinase (MAPK) signalling cascades, and PI3K/Akt pathways. Therefore, the aim of the present review was to elaborate on the cellular and molecular mechanisms of the quercetin involved in the protection against AD.

Improvement of the functionality of pancreatic Langerhans islets via reduction of bacterial contamination and apoptosis using phenolic compounds.

OBJECTIVES: 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.

Correction to: An evidence-based review of the genotoxic and reproductive effects of sulfur mustard.

This is with reference to the note of the Editor-in-Chief of the Archives of Toxicology.

Comparative occurrence of diabetes in canine, feline, and few wild animals and their association with pancreatic diseases and ketoacidosis with therapeutic approach.

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 ß- 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.