Introducing Group Open-Book Exams as a Learning and Assessment Strategy in the Clinical Biochemistry Course for Medical Students.

BACKGROUND: Teachers constantly strive to obtain reliable and appropriate teaching and assessment methods to maximize the learning experience. This study aimed to introduce combined modified team-based learning and open-book exams (TBL/OBEs) as learning and assessment strategies in clinical biochemistry for medical students and assess students' perceptions. METHODS: Second-year medical students enrolled in the clinical biochemistry course were included in this study and subjected to TBL/OBE assessment. The assessment included two parts: the open-book format for half of the questions and the closed-book format for the other as a control. Upon completing the combined TBL/OBE session, the students were required to complete a structured survey to evaluate their perception of the experience. The data were gathered and analyzed. Data were presented as mean±standard error of the mean (SEM), and a p-value ≤0.05 was considered statistically significant. RESULTS: A total of 358 students completed the TBL/OBE and closed-book exam (CBE) and responded to the survey. Of these students, 76% preferred the OBE, and 84% thought it was a suitable learning method. On the one hand, the mean difficulty of the OBE format was 92.7±1.5 SEM, while, for the CBE, the mean difficulty was 88.7±1.9 SEM (p=0.015). On the other hand, the mean discrimination factor for OBE was 0.26±0.04 and, for the CBE, 0.41±0.04 SEM (p=0.0016). Males found the OBE questions easier (p=0.025) and less stressful (p=0.01). CONCLUSION: A combined model of modified TBL and OBE is a successful learning and assessment strategy in clinical biochemistry for medical students.

Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome.

Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II-IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.

The Effect of Chronic Laxative Use on Lipid Profile and HbA1c: A Hospital-Based Retrospective Study.

BACKGROUND: Laxatives are over-the-counter medications used as a treatment for constipation. The lipid-lowering effect of the long-term use of laxatives has been proposed. AIM: To investigate the possible impact of the chronic use of laxatives on serum lipid profile, body mass index (BMI), and hemoglobin A1c (HbA1c). METHODS: An observational retrospective cohort study was conducted to analyze data related to patients who received laxatives for six or 12 months or more in the KAUH database system. BMI, weight, cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and HbA1c data were collected retrospectively from hospital records for three time points: baseline, six months, and 12 months of laxative treatment from the starting date for each patient. RESULTS: A total of 106 patients' records fulfilled the inclusion criteria, 46 (43%) males with a mean age of 66 and 60 (57%) females with a mean age of 63. A significant decrease in plasma cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels was observed in those who used laxatives for 12 months. Furthermore, an overall BMI and ALT reduction was seen in the combined. On the other hand, HbA1c levels appeared to improve in the combined group but not statistically significant. The change in the cholesterol level could be observed in patients receiving statin treatment and those without, with no statistical significance between the two groups. CONCLUSION: Chronic laxative use for 12 months or more is associated with a decreased total and LDL-C level with no significant effect on high-density lipoprotein-cholesterol (HDL-C) levels. Additionally, there was a significant reduction in BMI and ALT. This effect is more prominent with combined therapy. Further multicentric studies on larger sample sizes are recommended to confirm our findings.

SOX9 Expression Is Increased in Alzheimer's Disease (AD) and Is Associated With Disease Progression and APOE4 Genotype: A Computational Approach.

INTRODUCTION:  Alzheimer's disease (AD) is a neurodegenerative disease characterized by depositions of amyloid-ß protein leading to neuronal loss. Despite our understanding of the disease several gaps remain, including the role of astrocytes and astrocytic genes in the disease development and progression. Recently, some reports have suggested that SOX9 transcription factor (TF), an important mediator of astrocyte differentiation and maturation, might be linked to AD. Using human AD publicly available dataset, we aimed to analyze SOX9 expression and its relation to disease. METHODOLOGY:  The AD gene expression data set was obtained from National Center for Bioinformatics-Gene Expression Omnibus (NCBI-GEO). The GSE48350 consisted of mRNA microarray data from 55 normal controls (173 samples) and 26 AD cases (81 samples) obtained, from four brain regions. The SOX9 expression profile and correlations were analyzed using the R2 Genomics Analysis and Visualization platform. RESULTS:  The SOX9 was significantly upregulated (p<0.001) in AD tissue compared to control cases. The increased expression appeared to be more in the entorhinal cortex (EC) and hippocampus (HC) regions. The SOX9 expression positively correlated with BRAAK stages (p<0.05). Interestingly in AD patients the SOX9 expression was significantly less in APOE3/3 genotypes compared with genotypes containing APOE4 allele. The SOX9 expression negatively correlated with oxidative phosphorylation genes which could suggest a metabolic role for the TF. CONCLUSION:  From these data we hypothesize that SOX9 acts as a metabolic regulator responding to lipid metabolism disruption associated with APOE4 genotypes. In turn, SOX9 expression could be associated with astrocyte maturation and survival in the disease contributing thus to disease burden and disease progression.

Exploring the Validity of Available Markers and Indices in the Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD) in People with Type 2 Diabetes in Saudi Arabia.

Nonalcoholic fatty liver disease (NAFLD) is common among Saudi patients with type 2 diabetes (T2DM). However, recommended clinical procedures to detect it are unavailable in many locations. Therefore, better and more available diagnostic biomarkers for NAFLD are needed. Various serum parameters were suggested, and algorithms that employ routine measurements in clinical practice have been developed for the prediction of fat stores in the liver in different populations. However, no such studies have been conducted on Saudis. We aimed to compare selected biochemical markers and calculated indices in T2DM patients diagnosed with NAFLD and patients without NAFLD to find the best markers associated with NAFLD. A cross-sectional study was employed to recruit 67 people with T2DM from endocrine outpatient clinics at King Abdul-Aziz University Hospital. NAFLD was detected by ultrasonography in 28 patients. Demographic information, anthropometric, and blood pressure (BP) measurements were taken. Fasting blood samples were obtained to measure glucose, glycated haemoglobin, lipid profile, liver function tests, and highly sensitive C-reactive protein. Fatty liver index, hepatic steatosis index, NAFLD-liver fat score, and triglyceride and glucose index were calculated. Following stepwise forward likelihood ratio regression with independent variables included in one model using binary logistic regression with age and waist circumference (WC) entered as covariates, elevated diastolic BP and low high-density lipoprotein- cholesterol remained significantly associated with NAFLD (p = 0.002 and 0.03, respectively). However, none of the investigated indices could be used to diagnose the disease adequately due to low specificity, even after calculating new cut-off values. Investigating novel markers and adjusting existing equations used to calculate indices to improve sensitivity and specificity in our population is needed.

Fibroblast Growth Factor 21: A More Effective Biomarker Than Free Fatty Acids and Other Insulin Sensitivity Measures for Predicting Non-alcoholic Fatty Liver Disease in Saudi Arabian Type 2 Diabetes Patients.

Background Non-alcoholic fatty liver disease (NAFLD) is more prevalent among individuals with type 2 diabetes (T2DM), elevating their risk of cardiovascular diseases (CVDs) and premature mortality. There is a need to modify treatment strategies to prevent or delay these adverse outcomes. Currently, there are no sensitive or specific biomarkers for predicting NAFLD in Saudi T2DM patients. Therefore, we aimed to explore the possibility of using fibroblast growth factor 21 (FGF-21), free fatty acids (FFAs), homeostatic model assessment for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) as possible markers. Methodology In this study, a total of 67 T2DM patients were recruited. NAFLD was detected by ultrasonography in 28 patients. Plasma glucose, FFAs, FGF-21, and serum insulin were measured in fasting blood samples. HOMA-IR and QUICKI were calculated. The means of the two groups with and without NAFLD were statistically compared. The receiver operating characteristics (ROC) curve and the area under the curve (AUC) were used to assess the ability to identify NAFLD. Results The mean levels of FGF-21 and HOMA-IR were significantly higher and that of QUICKI was significantly lower in patients with NAFLD than in those without (p < 0.001, p = 0.023, and p = 0.018, respectively). FGF-21 had the highest AUC to identify NAFLD (AUC = 0.981, 95% confidence interval = 0.954-1, P < 0.001). The AUCs for HOMA-IR, QUICKI, and FFA were <0.7. The highest sensitivity, specificity, positive likelihood ratio, and the lowest negative likelihood ratio were found when FGF-21 was used to predict NAFLD. Conclusions FGF-21 may be used as a biomarker to predict NAFLD in people with T2DM due to its high sensitivity and specificity compared to the other markers.

ABCA1 C69T Gene Polymorphism Association with Dysglycemia in Saudi Prediabetic Adults.

Studies suggest that ATP-binding cassette transporter A1 (ABCA1 C69T) polymorphism is associated with a decreased incidence of type 2 diabetes mellitus (T2DM) and that there is an association between ABCA1 C69T polymorphism and the risk of dyslipidemia in diabetic individuals. However, other studies contradict these suggestions. Therefore, we aimed to investigate the prevalence of ABCA1 C69T (rs1800977) gene polymorphism in a representative sample of the Saudi population not previously diagnosed with diabetes and its possible association with dyslipidemia and dysglycemia. A cross-sectional design was used to recruit nondiabetic adults of both genders from the Saudi population in Jeddah by employing a stratified, two-stage cluster sampling method. A total of 650 people (337 men and 313 women) were recruited. Demographic, dietary, and lifestyle variables, as well as medical history and family history of chronic diseases, were collected using a predesigned questionnaire. Fasting blood samples were taken for the determination of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and lipids profile, which were followed by a 1-h oral glucose tolerance test (OGTT). Real-time PCR technology was used to determine the ABCA1 C69T gene SNP (rs1800977). The T allele of ABCA1 C69T (rs1800977) was very frequent (TT in 44.9% and CT in 43.7%). There was a trend toward significance for a higher dysglycemia percentage in people with CT and TT genotypes (25.7%, and 23.3%, respectively) compared with CC genotypes (16.2%). In addition, FPG and 1-h plasma glucose were significantly higher in people with both TT and CT genotypes compared to CC genotypes. However, T allele was not associated with any dysregulation of lipid parameters.

The influence of antioxidant dietary-derived polyphenolic combination on breast cancer: Molecular study.

Breast cancer remains a leading cause of female mortality worldwide. Therefore, novel complementary treatments have been sought. Recently, there has been a growing interest in investigating the possible complementary effects of polyphenolic compounds against various malignancies. In the present study, using MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, the anticancer efficacy of a polyphenolic mixture (PFM) was investigated. PFM is composed of curcumin, resveratrol, epigallocatechin gallate, and quercetin. PFM treatment led to a dose-dependent inhibition of cell proliferation, with IC50 values of 25.9 ± 3 µg/ml and 29.4 ± 0.9 µg/ml for MCF-7 and MDA-MB-231 cells, respectively. In addition, PFM induced apoptosis in MDA-MB-231 cells and cell cycle arrest at the S phase in MCF-7 cells. Using RT-qPCR, PFM treatment was observed to result in significant downregulation of the oncogenic miR-155 (P < 0.05), as well as significant downregulation of the rate-limiting glycolytic enzyme, hexokinase 2 (HK2) (P < 0.05), while upregulating the expression of the zinc finger E-box binding homeobox 2 gene (P < 0.01). PFM was also found to exert an anti-migration effect in breast cancer cells using the wound healing assay, as well as significantly (P < 0.05) increasing the median survival of Ehrlich ascites carcinoma (EAC) tumor-bearing mice. These results suggest that PFM possesses potential antitumor effects against breast cancer. A possible mechanism of action could be due to PFM's effect in modulating the expression of the glycolytic enzyme HK2 through suppression of miR-155 in MCF-7 cells. Combining polyphenolic compounds that interact with one another could result in synergistic effects that potentially target various tumour hallmarks.

Colossolactone-G synergizes the anticancer properties of 5-fluorouracil and gemcitabine against colorectal cancer cells.

Several terpenoids were isolated from Ganoderma colossum with potential chemotherapeutic properties against different solid tumor cells. Herein, we further assessed the potential chemomodulatory effects of colossolactone-G to gemcitabine (GCB) and 5-fluorouracil (5-FU) against colorectal cancer cells. Colossolactone-G induced moderate cell killing effects against both HT-29 and HCT-116 cells, with IC50's of 90.5 ± 1.7 µM and 22.3 ± 3.9 µM, respectively. Equitoxic combination demonstrated a synergistic effect between colossolactone-G and GCB, or 5-FU with combination indices ranging from 0.22 to 0.67. Both GCB and 5-FU induced moderate cell cycle arrest at G0/G1-phase and S-phase. Despite colossolactone-G's lack of influence on cell cycle distribution, it significantly potentiated GCB- and 5-FU-induced cell cycle arrest. Similarly, colossolactone-G treatment alone did not induce pronounced apoptosis in both cell lines. However, 5-FU and GCB induced significant apoptosis which was further potentiated via combination with colossolactone-G. Furthermore, colossolactone-G significantly increased autophagic cell death response in both HCT-116 and HT-29 cells and potentiated 5-FU- and GCB-induced autophagic cell death. The influence of colossolactone-G alone or in combination with GCB or 5-FU on the apoptosis and autophagy were confirmed by qPCR analysis for the expression of several key apoptosis and autophagy genes such as, TRAIL, TP53INP1, BNIP3, hp62, ATG5, ATG7, Lamp2A and the golden standard for autophagy (LC3-II). In conclusion, a synergistic effect in terms of anticancer properties was observed when colossolactone-G was combined with 5-FU and GCB, where it influenced both apoptosis and autophagic cell death mechanisms.

Why do cancer cells break from host circadian rhythm? Insights from unicellular organisms.

It is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of the oxidative pentose phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode.

Evaluation of early biomarkers of renal dysfunction in diabetic patients.

OBJECTIVES: To evaluate 2 renal tubular enzymes; urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary N-acetyl-beta-D-glucosaminidase (uNAG), and serum Cystatin C as candidate biomarkers for early diagnosis of early stage of diabetic nephropathy (DB) in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia during the period between  May 2017 and May 2018 and was conducted on 86 patients with T2DM. Patients were classified according to their albumin/creatinine ratio (ACR) into 3 groups; a normal albuminuria group with ACR less than 30 mg/g creatinine, a moderately increased albuminuria group with ACR: 30-299 mg/g creatinine, and a severely increased albuminuria group with ACR ≥300 mg/g.  Healthy adults were recruited as a control group. Urine uNGAL, uNAG, and serum Cystatin C were measured in all patients. RESULTS: Compared with healthy control, diabetic patients with normal albuminuria excreted significantly higher levels of uNGAL (p less than 0.001). In addition, significantly elevated uNGAL, uNAG and cystatin C levels were observed in moderately increased albuminuria and severely increased albuminuria groups when compared to the control and normoalbuminuric groups (p less than 0.001). urinary neutrophil gelatinase-associated lipocalin, urinary N-acetyl-beta-D-glucosaminidase and Cystatin C showed a positive correlation with fasting blood glucose (FBG), HbA1c, duration of diabetes, urea, creatinine, and ACR. CONCLUSION: Our results indicated that uNGAL could be a sensitive biomarker for early renal dysfunction in diabetic patients while uNAG and serum Cystatin C might have prognostic value.

Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism.

Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC50 values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC50 values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects.

Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities.

The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Thymoquinone (TQ) is a naturally occurring compound with cumulative evidence of anti-cancer properties. In this study, we assessed the chemomodulatory potential of TQ to gemcitabine (GCB) against human breast adenocarcinoma (MCF-7), and ductal carcinoma (T47D) cells. TQ showed cytotoxic effects against MCF-7 and T47D with IC50's of 64.9 ± 14 µM and 165 ± 2 µM, respectively. The IC50's of GCB against MCF-7 and T47D were 0.9 ± 0.18 µM and 14.3 ± 2.8 µM and were significantly reduced after combination with TQ to 0.058 ± 12 µM and 2.3 ± 0.2 µM, respectively. The CI- values were indicative of synergism in MCF-7 and T47D cells (0.15 and 0.30, respectively). Further investigation showed that GCB caused significant anti-proliferative effect reflected by increasing cell population in S-phase in both cell lines. TQ potentiated GCB-induced anti-proliferative activity in both cell lines. GCB induced considerable apoptosis in T47D cell line, and TQ significantly increased GCB-induced apoptotic effects by 1.5 to 3.6 folds. Interestingly, GCB, TQ and their combination induced significant autophagic cell death in the apoptosis defected MCF-7 cells. In addition, TQ, GCB and their combination depleted breast cancer associated stem cell (CD44(+)/CD24(-)/(low)) clone within MCF-7 and T47D cells by 3.8% to 27.5%. In conclusion, TQ showed promising chemomodulatory effects to GCB against breast cancer cells via inducing apoptosis, necrosis and autophagy, in addition to depleting tumor associated resistant stem cell fraction.

miRNA in tumour metabolism and why could it be the preferred pathway for energy reprograming.

The current literature on the role of microRNA (miRNA) in tumour metabolism is growing, and a number of studies regularly confirm the impact miRNA can have in energy reprograming in tumours. However, there remains to be a lack of understanding of the larger perspective of the role of miRNA in the metabolism story. In the first part of this review, we provide a comprehensive and up-to-date description of the extensive role of miRNAs in tumour metabolism including glucose, lipid and amino acid metabolism. However, in the second part, we aim to provide a description of the multidimensional role miRNA can be playing in tumour metabolism. Of paramount importance is the role miRNA has in responding to metabolic cues and how it can alter cellular state and fate, including cancer stem cells, in response to such cues. In addition, exosomal miRNAs can provide means by which cells can communicate metabolic signals and messages with other cells within the tumour microenvironment, altering therefore the phenotype and functional capacity of these cells. With this expanding area of research better understanding of the role of miRNA in tumour metabolism in a mechanistic approach, and not only describing which miRNAs can effect which genes, can help to exploit the therapeutic implications behind the extensive role of miRNA in tumour metabolism.

Ramadan fasting in Saudi Arabia is associated with altered expression of CLOCK, DUSP and IL-1alpha genes, as well as changes in cardiometabolic risk factors.

BACKGROUND: During the fasting month of Ramadan, practicing Saudis develop severe disturbances in sleeping and feeding patterns. Concomitantly, cortisol circadian rhythm is abolished, diurnal cortisol levels are elevated and circulating levels of several adipokines are altered favouring insulin resistance. AIM: To examine changes in the expression of CLOCK and glucocorticoid-controlled genes, such as DUSP1 and IL-1α in Saudi adults before and during Ramadan, and to investigate possible associations with selected cardiometabolic risk factors. METHODS: Healthy young volunteers (5 females, 18 males; mean age +SEM = 23.2 +1.2 years) were evaluated before Ramadan and two weeks into it. Blood samples were collected at 9 am (±1 hour) and twelve hours later for determination of serum lipid profile, high sensitivity CRP (hsCRP), and adiponectin. The expression of CLOCK, DUSP1 and IL-1α was evaluated in circulating leukocytes. RESULTS: Mean levels of GGT and morning adiponectin decreased, while those of LDL-c/ HDL-c and atherogenic index (AI) increased significantly in Ramadan compared to Shabaan. There was no significant difference between morning and evening adiponectin during Ramadan, while the diurnal rhythm of hsCRP was lost. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan. Mean morning and evening DUSP1 mRNA levels showed significant increase during Ramadan compared to Shabaan, however, its diurnal rhythm was maintained. Morning IL-1α mRNA expression remained significantly higher than in the evening during Ramadan, but was markedly decreased compared to Shabaan. DISCUSSION: Ramadan fasting in Saudi Arabia is associated with improvements in some cardiometabolic risk factors, such as circulating GGT and hsCRP and leukocyte expression of IL-1α mRNA, suggesting that intermittent fasting might have a beneficial component. These benefits may be offset by the previously reported dysregulation in the circadian rhythm, excess glucocorticoid levels and action, and insulin resistance, explaining increased prevalence of cardiometabolic disorders and type 2 diabetes mellitus.

Recombinant viral vaccines for cancer.

Cancer arises from 'self' in a series of steps that are all subject to immunoediting. Therefore, therapeutic cancer vaccines must stimulate an immune response against tumour antigens that have already evaded the body's immune defences. Vaccines presenting a tumour antigen in the context of obvious danger signals seem more likely to stimulate a response. This approach can be facilitated by genetic engineering using recombinant viral vectors expressing tumour antigens, cytokines, or both, from an immunogenic virus particle. We overview clinical attempts to use these agents for systemic immunisation and contrast the results with strategies employing direct intratumoural administration. We focus on the challenge of producing an effective response within the immune-suppressive tumour microenvironment, and discuss how the technology can overcome these obstacles.