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1.
Biomed Pharmacother ; 142: 112012, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34388531

ABSTRACT

A high-fat diet (HFD) is linked with cytokines production by non-neuronal cells within the hypothalamus, which mediates metabolic inflammation. These cytokines then activate different inflammatory mediators in the arcuate nucleus of the hypothalamus (ARC), a primary hypothalamic area accommodating proopiomelanocortin (POMC) and agouti-related peptide (AGRP) neurons, first-order neurons that sense and integrate peripheral metabolic signals and then respond accordingly. These mediators, such as inhibitor of κB kinase-ß (IKKß), suppression of cytokine signaling 3 (SOCS3), c-Jun N-terminal kinases (JNKs), protein kinase C (PKC), etc., cause insulin and leptin resistance in POMC and AGRP neurons and support obesity and related metabolic complications. On the other hand, inhibition of these mediators has been shown to counteract the impaired metabolism. Therefore, it is important to discuss the contribution of neuronal and non-neuronal cells in HFD-induced hypothalamic inflammation. Furthermore, understanding few other questions, such as the diets causing hypothalamic inflammation, the gender disparity in response to HFD feeding, and how hypothalamic inflammation affects ARC neurons to cause impaired metabolism, will be helpful for the development of therapeutic approaches to prevent or treat HFD-induced obesity.


Subject(s)
Diet, High-Fat/adverse effects , Inflammation/pathology , Obesity/physiopathology , Animals , Arcuate Nucleus of Hypothalamus/pathology , Cytokines/metabolism , Female , Humans , Inflammation/etiology , Inflammation Mediators/metabolism , Male , Neurons/metabolism , Obesity/etiology , Obesity/therapy , Sex Factors
3.
Environ Sci Pollut Res Int ; 28(40): 56319-56332, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34050519

ABSTRACT

Cisplatin, an anticancer drug used in treating various types of cancers, can cause reproductive toxicities during chemotherapy. Keeping this in view, the present study was designed to investigate the possible protective effects of normal vitamin C and E and vitamin C and E nanoparticles (embedded in chitosan) against cisplatin-induced reproductive toxicities. Vitamins C, E, and their nanoparticles in this regard proved to be an effective therapy. The work aimed to treat cisplatin-induced reproductive toxicities through vitamin C and E and their nanoparticles. Cisplatin exposure caused significant reduction in the weight, testosterone level, and changed lipid profile. Similarly, cisplatin induced significant widespread testicular atrophy and testicular lesions as evidenced by the gaps in the epithelium and loss of differentiating germ cells. Vitamin C and E and their nanoparticles rescued the weight, testosterone level, and testicular disturbances, which is associated with improved histological view of testicular tissues. The current study highlights evidence that designing a medication of vitamin C and E nanoparticles is useful in mitigating cisplatin-induced reproductive toxicity in cancerous male patients underlying chemotherapy.


Subject(s)
Chitosan , Nanoparticles , Androgens , Animals , Antioxidants , Ascorbic Acid , Cisplatin/toxicity , Humans , Male , Rats , Testis , Vitamin E , Vitamins
4.
Mikrochim Acta ; 188(5): 177, 2021 04 28.
Article in English | MEDLINE | ID: mdl-33907901

ABSTRACT

Nanocomposites can offer a platform to conjugate biorecognition features of aptamer with unique size-dependent properties of a given material, which can autoprobe the binding event based on their electroactive characteristics. Herein, we design electroactive switchable aptamer probes based on co-doped single-phase semiconducting materials employing the cyclic voltammetry method to record the current signal at each step of electrochemical characterization. To do so, we utilized a facile hydrothermal method assisted by co-precipitation method such as Co-Fe-co-doped Ba0.5Sr0.5Zr0.1Y0.1O3-δ (CF-BSZY) and tuned the alignment of the energy band structure of the material to amplify the output of the electrochemical signal. At various steps, changes occurred in the electrochemical properties at the surface of CF-BSZY. The binding of the ssDNA with prepared materials enhances the current signal by the interaction with the target (ochratoxin A (OTA)) depressing the current signal and facilitating the construction of a novel design of electrochemical aptasensor. As a proof of concept, an electrochemical aptasensor for the detection of ochratoxin A (OTA) in rice samples has been developed. The electrochemical aptasensor provides a limit of detection (LOD) of 0.00012 µM (0.12 nM), with a linear range from 0.000247 to 0.74 µM and sound OTA recovery in real samples. The developed aptasensor is simply designed and is free of oligonucleotide labeling or decorative nanoparticle modifications. The proposed mechanism is generic in principle with the potential to translate any type of aptamer and target binding event into a detectable signal; hence, it can be largely applied to various bioreceptor recognition phenomena for subsequent applications.


Subject(s)
Aptamers, Nucleotide/chemistry , Metals, Heavy/chemistry , Ochratoxins/analysis , Semiconductors , Biosensing Techniques/methods , DNA, Single-Stranded/chemistry , Electrochemical Techniques/methods , Food Contamination/analysis , Limit of Detection , Ochratoxins/chemistry , Oryza/chemistry , Proof of Concept Study , Reproducibility of Results
5.
Article in English | MEDLINE | ID: mdl-31781033

ABSTRACT

Puberty generally occurs when an individual has stored a sufficient amount of energy. Previous reports have shown that postnatal overfeeding, induced by a small litter size or maternal high fat diet (HFD) feeding during gestation and lactation increases body weight (BW), body fat, plasma leptin levels, and induces precocious puberty. The role of BW, body fat, and leptin in postnatal HFD-induced precocious puberty is poorly understood. In this study, we investigated if postnatal HFD feeding induces precocious puberty independent of BW, body fat, and leptin levels. Different litter sizes and different exposure time to HFD were used to produce HFD feeding pups with different BW and body fat. BW, body fat, and plasma hormones levels were checked at different time points to test their relation with HFD-induced precocious puberty. Our results showed that postnatal HFD feeding increases BW, body fat, adipocyte size, and induces precocious puberty. HFD-induced precocious puberty was independent of BW, body fat, and plasma leptin levels. Plasma gonadotrophin, estradiol, testosterone and insulin levels were comparable in most of the groups. Our results collectively suggest that postnatal HFD feeding induces precocious puberty independent of BW, body fat and plasma leptin levels. Our results also suggest that HFD feeding acts as a stimulator for puberty onset but further studies are needed to understand how it induces precocious puberty.

6.
Int J Biol Sci ; 15(2): 265-276, 2019.
Article in English | MEDLINE | ID: mdl-30745819

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is an acquired metabolic disease characterized by triglycerides (TGs) deposition in liver induced by other factors rather than alcohol consumption. NAFLD significantly contributes to liver diseases in children and adults. NAFLD pathogenesis is associated with age, gender, race and ethnicity. Insulin resistance, hyperinsulinemia, elevated plasma free fatty acids (FFAs), fatty liver, hepatocyte injury, liver inflammation, oxidative stress, mitochondrial dysfunction, imbalanced pro-inflammatory cytokines, and fibrosis are the characteristics of NAFLD. Factors including genetic and epigenetic pathways, sedentary lifestyle, sleep, and diet composition affect NAFLD pathogenesis. In this review, we discuss the aetiology, risk factors and pathogenesis of NAFLD. Special focus is given to macro and micro nutrition as causing factors and their role in the prevention of NAFLD pathogenesis.


Subject(s)
Inflammation/immunology , Inflammation/metabolism , Liver/immunology , Liver/metabolism , Non-alcoholic Fatty Liver Disease/immunology , Non-alcoholic Fatty Liver Disease/metabolism , Fatty Acids, Nonesterified/blood , Humans , Inflammation/blood , Non-alcoholic Fatty Liver Disease/blood , Oxidative Stress/physiology , Risk Factors
7.
J Ovarian Res ; 10(1): 62, 2017 Sep 15.
Article in English | MEDLINE | ID: mdl-28915843

ABSTRACT

BACKGROUND: PCOs is a heterogeneous disorder with anovulation/oligo ovulation usually taken as oligo menorrhoea or amenorrhoea, hyperandrogenemia, hirsutism, acne, androgen alopecia and polycystic ovaries as the key diagnostic feathers. The study was undertaken to investigate the possible protective and ameliorating effects of GABA in Letrozole induced PCOS model in rats by targeting insulin resistance. METHODS: PCOs in Adult female rat was induced by the daily gastric administration of letrozole (1 mg/kg/day) in CMC (0.5%) for 36 days. Rats were given metformin (2 mg/kg), GABA (100 mg/kg/day) and GABA (500 mg/kg/day) along with letrozole. One group severed as vehicle control. On the 37 day, the animals were euthanized, and anthropometrical, biochemical (glucose, insulin, lipids, testosterone, Estradiol, Progesterone, oral glucose tolerance test, total protein content in ovary, cholesterol level, triglyceride, HDL, LDL), Antioxidants (CAT, POD, GSR, ROS, GSH, TBARS), and histopathological evaluation of ovaries were carried out. Daily colpocytological examination was also carried out until the termination. RESULTS: Both the doses of GABA significantly reduced body weight, body mass index and testosterone. While the levels of CAT, SOD, POD and Estradiol (E2) were significantly increased in the both doses of GABA. A favourable lipid profile, normal glucose tolerance, and decreased in the percentage of estrus smears were observed. Histopathological examination of ovary revealed a decreased in the number of cystic follicles, and decreased in the adipocytes respectively. The effects observed with GABA were comparable to that with metformin. CONCLUSION: The results suggest that GABA treatment has shown protective effect in PCOs and provide beneficial effect either by reducing insulin resistance or by inducing antioxidant defence mechanisms.


Subject(s)
Androgen Antagonists/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Protective Agents/therapeutic use , gamma-Aminobutyric Acid/therapeutic use , Androgen Antagonists/pharmacology , Animals , Blood Glucose/analysis , Body Weight/drug effects , Catalase/metabolism , Estradiol/blood , Female , Insulin Resistance , Letrozole , Nitriles , Ovary/drug effects , Ovary/metabolism , Ovary/pathology , Peroxidase/metabolism , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Protective Agents/pharmacology , Rats , Reproduction/drug effects , Superoxide Dismutase/metabolism , Testosterone/blood , Triazoles , gamma-Aminobutyric Acid/pharmacology
8.
Front Med ; 11(2): 266-276, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28500430

ABSTRACT

Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet (HFD) to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight (BW) of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet-induced postnatal childhood obesity and puberty.


Subject(s)
Diet, High-Fat/adverse effects , Obesity/etiology , Puberty, Precocious/etiology , Animals , Animals, Newborn , Female , Kisspeptins/metabolism , Lactation , Male , Mice , Mice, Inbred C57BL , Sexual Maturation , Weaning , Weight Gain
9.
Environ Sci Pollut Res Int ; 23(13): 12932-40, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26996903

ABSTRACT

The present study was designed to study the effect of brick kilns emissions on the reproductive health and biochemical status of brick kiln workers and people living in the area near brick kilns. Body mass index (BMI) was significantly reduced in brick makers, carriers, and bakers compared to the control. Red blood cells count and hematocrit (%) were significantly high in brick bakers while MCH was significantly reduced in brick makers and brick bakers. Heavy metals (lead, cadmium, and chromium) concentration in whole blood of the brick kiln workers were significantly higher as compared to the control. Antioxidant enzymes (CAT, SOD, POD, GSH, and GR) were significantly reduced in brick kiln workers as compared to the control while TBARS level were significantly high in brick bakers as compared to the control. Plasma leutinizing hormone (LH) was significantly high in brick bakers while testosterone concentrations were significantly reduced in brick makers, carriers, and bakers. The present study shows that brick kiln workers and people living in the brick kiln vicinity are exposed to heavy metals and other pollutants that is a serious threat to their health. Alternate technology is needed to be developed and brick kilns should be replaced.


Subject(s)
Antioxidants/metabolism , Construction Materials/adverse effects , Metals, Heavy/adverse effects , Occupational Exposure , Reproductive Health , Adult , Body Mass Index , Environmental Pollutants/adverse effects , Humans , Male , Middle Aged , Pakistan , Young Adult
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