The association between fat mass and obesity-associated (FTO) genotype and serum vitamin D level in breast cancer patients.

The preventive effect of vitamin D against breast cancer can be influenced by gene polymorphisms. This study aimed to investigate the association between serum level of 25(OH) vitamin D and FTO genotype in breast cancer patients. A cross-sectional study was carried out on 180 newly diagnosed patients with breast cancer in Tehran, Iran. The blood samples were collected from the participants in order to assess the FTO gene rs9939609 polymorphism by the tetra-primer amplification refractory mutation system (Tetra-ARMS) PCR method. The serum level of 25(OH) vitamin D was measured using the direct competitive enzyme-linked immunosorbent assay (ELISA) method. The association between vitamin D and the FTO genotype in patients with breast cancer was assessed after adjustment for cofounders. The frequency of TT, AT and AA genotypes in the breast cancer patients were 43% (n = 77), 49% (n = 89) and 8% (n = 14), respectively. All patients with higher than 40 ng/dl of serum 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele (p = 0.019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer.

An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.

Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer's disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.

Targeting LIN28: a new hope in prostate cancer theranostics.

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.

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells.

Adenosine receptor-mediated regulation of monocyte/macrophage inflammatory responses is critical in the maintenance of tissue homeostasis. In this study, we reveal that adenosine potently modulates the expression of NR4A1, 2, and 3 orphan nuclear receptors in myeloid cells, and this modulation is primarily through the adenosine A2a receptor subtype. We demonstrate that A2a receptor activation of NR4A1-3 receptor synthesis is further enhanced in TLR4-stimulated monocytes. After TLR4 stimulation, NR4A receptor-depleted monocyte/macrophage cells display significantly altered expression of cell-surface markers and produce increased inflammatory cytokine and chemokine secretion rendering the cells an enhanced proinflammatory phenotype. Exposure of TLR4 or TNF-α-stimulated monocytes to adenosine analogs directs changes in the expression of MIP-3α and IL-23p19, with NR4A2 depletion leading to significantly enhanced expression of these factors. Furthermore, we establish that nuclear levels of NF-κB/p65 are increased in TLR/adenosine-stimulated NR4A2-depleted cells. We show that, after TLR/adenosine receptor stimulation, NR4A2 depletion promotes significant binding of NF-κB/p65 to a κB consensus binding motif within the MIP-3α proximal promoter leading to increased protein secretion, confirming a pivotal role for NF-κB activity in controlling cellular responses and gene expression outcomes in response to these mediators. Thus, these data demonstrate that during an inflammatory response, adenosine modulation of NR4A receptor activity acts to limit NF-κB-mediated effects and that loss of NR4A2 expression leads to enhanced NF-κB activity and hyperinflammatory responses in myeloid cells.

The effect of consuming Palmaria palmata-enriched bread on inflammatory markers, antioxidant status, lipid profile and thyroid function in a randomised placebo-controlled intervention trial in healthy adults.

PURPOSE: Palmaria palmata (P. Palmata) is reported to contain anti-inflammatory and antioxidant compounds albeit no study has investigated these effects in humans. METHODS: A randomised parallel placebo-controlled human intervention study was carried out to investigate the effect of consuming P. Palmata (5 g/day) incorporated into a bread on serum markers of inflammation [C-reactive protein (CRP); cytokine analysis] with secondary analysis investigating changes in lipids (cholesterol, triglycerides), thyroid function [thyroid-stimulating hormone (TSH)] and antioxidant status ferric reducing antioxidant power. ANCOVA with baseline values as covariates, controlling for age, BMI, sex and smoking status, was used to compare differences between treatment groups over time . In vitro studies investigated the inflammatory activity of P. Palmata extracts (hot water, cold water and ethanol extract), protein extracts and associated protein hydrolysates using a Caco-2 inflammation cell model. RESULTS: Consumption of P. Palmata-enriched bread significantly increased serum CRP (+16.1 %, P = 0.011), triglycerides (+31.9 %, P = 0.001) and TSH (+17.2 %, P = 0.017) when compared to the control group. In vitro evaluation of P. palmata extracts and protein hydrolysates identified a significant induction of IL-8 secretion by Caco-2 cells, and the hot water P. palmata extract was shown to increase adipocyte glycerol release (P < 0.05). CONCLUSION: Evidence from this human study suggests that P. palmata stimulates inflammation, increases serum triglycerides and alters thyroid function; however, these changes are not likely to impact health as changes remained within the normal clinical range. The data from the in vitro study provided indications that IL-8 may contribute to the apparent immunostimulation noted in the human study.

The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages.

Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1 macrophages. Extracts contained 34%-42% total fatty acids as n-3 PUFA and 5%-7% crude extract as pigments, including chlorophyll a, ß-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p < 0.05) and IL-8 (p < 0.05) while that of P. lutheri inhibited IL-6 (p < 0.01) production. Quantitative gene expression analysis of a panel of 92 genes linked to inflammatory signaling pathway revealed down-regulation of the expression of 14 pro-inflammatory genes (TLR1, TLR2, TLR4, TLR8, TRAF5, TRAF6, TNFSF18, IL6R, IL23, CCR1, CCR4, CCL17, STAT3, MAP3K1) by the lipid extracts. The lipid extracts effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases.

Isotopic turnover of carbon and nitrogen in bovine blood fractions and inner organs.

RATIONALE: Isotope ratio analysis of bovine tissues is a tool for inferring aspects of the dietary history of cattle. The objective of this experiment was to quantify the carbon (C) and nitrogen (N) isotopic turnover in blood (serum and residue) and inner organs (liver, kidney, heart and brain) of beef cattle. METHODS: Growing beef cattle (n = 70 in total) were either switched from a control diet containing barley and urea to an experimental diet containing maize and (15)N-enriched urea, for various intervals prior to slaughter or maintained on the control diet for 168 days pre-slaughter. Samples of blood, liver, kidney, heart and brain were collected at 0, 14, 28, 56, 112 and 168 days and analysed using Isotope Ratio Mass Spectrometry. RESULTS: After 168 days, C- and N-isotopic equilibrium was reached in the blood serum, liver and kidney, approached in the heart and brain, but not reached in the non-serum component of blood. The estimated C and N half-lives were 16.5 and 20.7 days for liver, 19.2 and 25.5 days for kidney, 29.2 and 35.6 days for blood serum, 37.6 and 49.9 days for heart, 53.3 and 52.2 days for brain and 113.3 and 115.0 days for the non-serum blood residue, respectively. Modelling the C and N turnover in the different tissue combinations revealed that a combined analysis of liver and heart as well as brain and kidney can provide the most accurate estimation of the timing of the diet switch. CONCLUSIONS: Based on the difference in turnover rates, bovine soft tissues can provide isotopic information on short- and long-term dietary changes, which in turn may be linked to the geographic or production origin of beef cattle. This study also provides basic biological data on organ C and N turnover in a large herbivorous mammal.

The association between enteral nutrition with survival of critical patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in several complications and mortality in intensive care unit (ICU) patients. Limited studies have investigated the effect of enteral nutrition (EN) on the survival of COVID-19 patients in the ICU. The aim of this study was to investigate the association of EN with biochemical and pathological indices associated with mortality in ICU patients with COVID-19. METHODS: This case-control study was conducted on 240 patients with COVID-19 hospitalized in the ICU including 120 eventual nonsurvived as the cases and 120 survived patients as the controls. All of the patients received EN as a high protein high volume or standard formula. Data on general information, anthropometric measurements, and the results of lab tests were collected. RESULTS: The recovered patients received significantly more high protein (60.8% vs. 39.6%, p = .004) and high volume (61.6% vs. 42.3%, p = .005) formula compared to the nonsurvived group. Mortality was inversely associated with high volume (odds ratio [OR]: 0.45 confidence interval [CI]95%, p = .008) and high protein (OR: 0.42 CI95%, p = .003) formula. The results remained significant after adjusting for age and sex. Further adjustment for underlying diseases, smoking, body mass index, and the acute physiology and chronic health evaluation II (APACHE II) score did not change the results. CONCLUSION: The findings of the study showed that there was a significant inverse association between mortality and high volume and high protein formula in patients with COVID-19. Further investigation is warranted.

Efficacy of a Comprehensive Weight Reduction Intervention in Male Adolescents With Different FTO Genotypes.

BACKGROUND: The FTO gene polymorphisms may influence the effects of lifestyle interventions on obesity. The present study aimed to assess the influence of the rs9930506 FTO gene polymorphism on the success of a comprehensive weight loss intervention in male adolescents with overweight and obesity. METHODS: This study was carried out on 96 adolescent boys with overweight and obesity who were randomly assigned to the intervention (n = 53) and control (n = 43) groups. The blood samples of the participants were collected, and the FTO gene was genotyped for the rs9930506 polymorphism. A comprehensive lifestyle intervention including changes in diet and physical activity was performed for 8 weeks in the intervention group. RESULTS: Following the lifestyle intervention, BMI and fat mass decreased significantly in the intervention group compared with the control group (both p < 0.05), while no change was found in weight, height or body muscle percentage between the groups. The participants in the intervention group with the AA/AG genotype and not in carriers of the GG genotype had a significantly higher reduction in BMI (-1.21 vs. 1.87 kg/m2, F = 4.07, p < 0.05) compared with the control group. CONCLUSION: The intervention in individuals with the AA/AG genotype has been significantly effective in weight loss compared with the control group. The intervention had no association effect on anthropometric indices in adolescents with the GG genotype of the FTO rs9930506 polymorphism. TRIAL REGISTRATION: Name of the registry: National Nutrition and Food Technology Research Institute; Trial registration number: IRCT2016020925699N2; Date of registration: 24/04/2016; URL of trial registry record: https://www.irct.ir/trial/21447.

The effect of FTO gene rs9939609 polymorphism on the association between colorectal cancer and different types of dietary fat intake: a case-control study.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. Some dietary factors such as fat intake have been identified as the risk factors for CRC. This study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene rs9939609 polymorphism on the association between CRC and different types of dietary fats. METHODS: This case-control study was performed on 135 CRC cases and 294 healthy controls in Tehran, Iran. Data on demographic factors, anthropometric measurements, physical activity, the intake of different types of dietary fats, and FTO gene rs9939609 polymorphism was collected from all participants. The association between cancer and dietary fat intake in individuals with different FTO genotypes was assessed using different models of logistic regression. RESULTS: Oleic acid intake was higher in the case group compared to the control group in both people with TT (7.2±3.46 vs. 5.83±3.06 g/d, P=0.02) and AA/AT genotypes (8.7±6.23 vs. 5.57 ±3.2 g/d, P<0.001). Among carriers of AA/AT genotypes of FTO rs9939609 polymorphism, a positive association was found between CRC and higher intakes of oleic acid (OR=1.12, CI95% 1.03-1.21, P=0.01) and cholesterol (OR=1.01, CI95% 1.00-1.02; P=0.01) after adjusting for age, sex, physical activity, alcohol use, smoking, calorie intake, and body mass index. CONCLUSION: Higher intakes of cholesterol and oleic acid were associated with a higher risk of CRC in FTO-risk allele carriers. The association of CRC and dietary fat may be influenced by the FTO genotype. Further longitudinal studies are warranted to confirm these findings.

The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID-19: A case-control study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) has become a worldwide health issue with widespread hospitalization and dependence on the intensive care unit (ICU). Vitamin D has a key role in modulating immune cells and modulating the inflammatory responses. This study aimed to investigate the association of vitamin D supplementation with inflammatory, biochemical, and mortality indices in critically ill patients with COVID-19. METHODS: This case-control study was conducted on critically ill COVID-19 patients hospitalized in the ICU including the survived >30 day patients as the case group and dead patients as the control group. The status of vitamin D supplementation and inflammatory and biochemical indices of the patients were retrieved from the medical records. Logistic regression method was used to assess the association between 30 days survival and vitamin D supplement intake. RESULTS: Compared to the group of COVID-19 patients who died in <30 day, the survived patients had a lower eosinophile level (2.2 ± 0.5 vs. 6 ± 0.0, p < .001) and higher vitamin D supplementation duration (9 ± 4.4 vs. 3.3 ± 1.9 day, p = .001). Vitamin D supplementation had a positive association with survival in COVID-19 patients (OR: 1.98, 95% CI: 1.15-3.40, p < .05). The association remained significant after adjustments fot age, sex, underlying diseases, and smoking. CONCLUSION: Vitamin D supplementation in critically ill patients with COVID-19 has the potential to increase survivability within the first 30 days of hospitalization.

Association between type 2 diabetes and branched chain amino acids (BCAA); a case-control study.

Background: Several amino acids and their derivatives have been implicated in insulin resistance (IR) and Type 2 Diabetes Mellitus (T2DM). This research sought to establish a relationship between the dietary levels of branched-chain amino acids (BCAA) and the risk of T2DM. Methods: This case-control study was carried out on 4200 participants consisting of 589 people with T2DM and 3611 non-diabetic aged 35 to 70 years residents in Sabzevar, Iran. Data on the economic-social, employment status, medical history, lifestyle, and sleep habits were collected via interview. The food frequency questionnaire (FFQ) was used to check the nutritional status. Participants' dietary BCAA consumption was estimated using Nutritionist IV software. Results: A significant negative association between the incidence of T2DM and the dietary levels of BCAAs after adjustment for age and sex (OR = 0.972, CI 95%:0.648-0.996, P = 0.022). The negative association remained significant after additional adjustments for body mass index (BMI) and physical activity (OR = 0.967, CI 95%: 0.943-0.992, P = 0.010). Interestingly, a positive association was found between T2DM and total BCAAs (OR = 1.067, CI 95%: 1.017-1.119, P = 0.008), Isoleucine (OR = 1.248, CI 95%: 1.043-1.494, P = 0.016), Leucine (OR = 1.165, CI 95%: 1.046-1.299, P = 0.006) and Valine (OR = 1.274, CI 95%: 1.088-1.492, P = 0.003) after further adjustment for calorie intake. Conclusions: Our results demonstrate branched-chain amino acids (BCAAs) including isoleucine, leucine, and valine are negatively associated with the incidence of type 2 diabetes (T2DM) after adjusting for age and sex, BMI, and physical activity. However, adjusting for calorie intake reversed the association between T2DM and BCAAs. These findings suggest that the association between BCAAs and T2DM may be influenced by calorie intake. Future longitudinal studies are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01247-9.

Gene Therapy for Neuropsychiatric Disorders: Potential Targets and Tools.

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.

A molecular approach to identification and profiling of first-line-drug-resistant mycobacteria from sputum of pulmonary tuberculosis patients.

Conventional and molecular techniques were applied to detect and characterize drug resistance of mycobacteria in the sputum samples of clinically confirmed tuberculosis. The sensitivities of mycobacterium detection by ZN staining, culture, multiplex PCR, and restriction fragment length polymorphism (RFLP) were 27.7%, 19.9%, 92.9%, and 95.7%, respectively, but all were 100% specific. The conventional and multiple-allele-specific PCR (MAS-PCR) methods enabled establishment of the drug resistance in 19.3% and 86.9% cases, respectively. We demonstrated that molecular techniques have potential in the accurate diagnosis of tuberculosis.

Analysis of multiple polymorphisms in the bovine neuropeptide Y5 receptor gene and structural modelling of the encoded protein.

The neuropeptide Y 5 receptor (NPY5R) plays an important role in the regulation of appetite and feeding behaviour in mammals by modulating the effect of the neurotransmitter neuropeptide Y. As single nucleotide polymorphism (SNP) variation in the bovine NPY5R gene is likely to influence the expression and/or function of this gene, the objectives of this study were to identify SNPs in the bovine NPY5R gene and to predict their functional role in the expression and physico-chemical characteristics of the protein product. Nineteen novel SNPs were identified in a 2.1 kb genomic region of the NPY5R gene in a total of 419 beef cattle from 13 Bos taurus breeds and eight Bos indicus animals. Four of these SNPs were non-synonymous (Met â†’ Ile, Leu â†’ Phe, Pro â†’ Leu, Arg â†’ Stop codon), while 10 were synonymous. Of particular interest was one non-synonymous SNP (c.1090C>T) that introduced a stop codon in the third intracellular loop of the NPY5R molecule. This stop codon is predicted to create a truncated NPY5R molecule with different physico-chemical properties compared to the native NPY5R protein. A further four SNPs were located in the 5' untranslated region (UTR) and one in the 3'UTR. Two of the 5'UTR SNPs affected putative transcription factor binding sites (GATA binding factor and snRNA-activating protein complex). In conclusion, regulatory and functional SNPs were identified in the bovine NPY5R gene. These include SNPs which potentially modify transcription factor binding sites as well as SNPs that cause amino acid changes and premature termination of the NPY5R protein. Such polymorphisms are likely to play vital physiological roles in the neuropeptide Y mediated appetite, feed intake and energy homeostasis in cattle.

Functional characterisation of the bovine neuropeptide Y gene promoter and evaluation of the transcriptional activities of promoter haplotypes.

Neuropeptide Y (NPY) is a potent orexigenic agent. The molecular mechanisms underlying the regulation of bovine NPY gene expression by its promoter region is currently unknown. The objectives of this research were to: (i) identify the SNPs in the promoter region of the bovine NPY gene, (ii) investigate the effects of these SNPs by measuring promoter transcriptional activities of different bovine NPY promoter haplotypes and; (iii) identify the minimal promoter region (MPR) required for basal activity of the NPY gene in vitro. Seventeen SNPs were identified in the promoter region. Of these, 14 affected putative transcription factors binding motifs including a TATA binding protein factor at -20, GC-Box factors SP1 at -170 and GATA binding motifs at -120 and -347. The SNPs were assigned to five major haplotypes (BtNPY_H1-5), of which BtNPY_H5 had maximum transcriptional activity. The region extending to -134 nt was identified as the MPR. This MPR was confirmed by the identification of a putative TATA box (-29 nt) and two SP1/GC binding sites (-94 and -118 nt), within this region. However, promoter expression was significantly enhanced when the construct contained the -614 to -1019 nt region. In conclusion, a number of SNPs characterised in the bovine NPY promoter especially those affecting the transcription factor binding sites, enhancer and repressor regions have the potential to affect NPY gene expression. Natural variation exists in the promoter region of the bovine NPY gene, which should be further explored for selection of energetic efficiency in cattle.

Breast cancer and dietary fat quality indices in Iranian women: A case-control study.

Background: The association between breast cancer (BC) and different indices of dietary fats has not been well-studied. Thus, this study aimed to investigate the association between BC and dietary fat quality (DFQ) indices in Iranian women. Methods: This case-control study was conducted on 120 women with breast cancer and 240 healthy women in Tehran, Iran. Food Frequency Questionnaire and nutritionist IV software were used to assess the intake of dietary fats and to calculate the DFQ indices. Results: The patients with BC had a higher total fat (TF) (P < 0.01) and a lower ratio of polyunsaturated fatty acids (PUFAs) omega-3 to PUFAs omega-6 (ω-3/ω-6) compared with the controls (P < 0.001). TF had a significant association with BC risk (OR: 1.16; 95% CI: 1.01-1.33, P < 0.001). No significant association was found between BC and PUFA/saturated fatty acid ratio or the ω-3/ω-6 ratio. Conclusion: The patients with BC had a lower ω-3/ω-6 ratio and a higher total dietary fat intake than the healthy women. Total dietary fat intake was also directly associated with the risk of BC. Thus, low-fat diets may have beneficial effects for BC prevention. Further longitudinal studies are warranted.

Overview of therapeutic targets in management of dementia.

Dementia is defined as a gradual cognitive impairment that interferes with everyday tasks, and is a leading cause of dependency, disability, and mortality. According to the current scenario, millions of individuals worldwide have dementia. This review provides with an overview of dementia before moving on to its subtypes (neurodegenerative and non-neurodegenerative) and pathophysiology. It also discusses the incidence and severity of dementia, focusing on Alzheimer's disease with its different hypotheses such as Aß cascade hypothesis, Tau hypothesis, inflammatory hypothesis, cholinergic and oxidative stress hypothesis. Alzheimer's disease is the most common type and a progressive neurodegenerative illness distinct by neuronal loss and resulting cognitive impairment, leading to dementia. Alzheimer's disease (AD) is considered the most familiar neurodegenerative dementias that affect mostly older population. There are still no disease-modifying therapies available for any dementias at this time, but there are various methods for lowering the risk to dementia patients by using suitable diagnostic and evaluation methods. Thereafter, the management and treatment of primary risk elements of dementia are reviewed. Finally, the future perspectives of dementia (AD) focusing on the impact of the new treatment are discussed.

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.

A potential role of IL-6 in the chito-oligosaccharide-mediated inhibition of adipogenesis.

Recent studies have suggested that chito-oligosaccharides can have anti-adipogenic properties. The objectives of the present study were to evaluate the anti-adipogenic potential of four different chito-oligosaccharides (molecular weight (MW) < 1000, 1000-3000, 3000-5000 and 5000-10,000 Da) and to identify molecular mechanisms underlying the chito-oligosaccharide-mediated inhibition of adipogenesis. Mouse 3T3-L1 cells were allowed to differentiate in the presence of chito-oligosaccharide. At day 8 post-induction of differentiation, lipid accumulation, free glycerol release and the quantitative expression of adipogenic marker genes were evaluated. Chito-oligosaccharides had concentration- and MW-dependent inhibitory effects on lipid accumulation (P < 0·001 and < 0·05, respectively), as well as a concentration-dependent effect (P < 0·001) on free glycerol release and the expression of adipogenic marker genes. The 5000-10,000 Da chito-oligosaccharide was selected for subsequent molecular studies. A panel of forty-four lipid metabolic pathway-specific genes was analysed by quantitative real-time PCR. Chito-oligosaccharide-mediated inhibition of adipogenesis was associated with the up-regulation of the IL-6 gene at all concentrations of chito-oligosaccharide examined and the PG-endoperoxide synthase 2 (PTGS2) gene at higher concentrations of chito-oligosaccharide. The effect of chito-oligosaccharide on gene expression was validated by measuring IL-6 protein concentrations in the media. Finally, an IL-6 promoter assay was developed to characterise the effect of chito-oligosaccharide on the transcriptional activity of the IL-6 promoter, which was increased in a concentration-dependent manner (P < 0·001). We conclude that IL-6 is a candidate signalling molecule in the chito-oligosaccharide-mediated inhibition of adipogenesis in 3T3-L1 cells.