How do we change our approach to COVID with the changing face of disease?

INTRODUCTION: The emergence of SARS-CoV-2 triggered a global health emergency, causing > 7 million deaths thus far. Limited early knowledge spurred swift research, treatment, and vaccine developments. Implementation of public health measures such as, lockdowns and social distancing, disrupted economies and strained healthcare. Viral mutations highlighted the need for flexible strategies and strong public health infrastructure, with global collaboration crucial for pandemic control. AREAS COVERED: (i) Revisiting diagnostic strategies, (ii) adapting to the evolving challenge of the virus, (iii) vaccines against new variants, (iv) vaccine hesitancy in the light of the evolving disease, (v) treatment strategies, (vi) hospital preparedness for changing clinical needs, (vii) global cooperation and data sharing, (viii) economic implications, and (ix) education and awareness- keeping communities informed. EXPERT OPINION: The COVID-19 crisis forced unprecedented adaptation, emphasizing public health readiness, global unity, and scientific advancement. Key lessons highlight the importance of adaptability and resilience against uncertainties. As the pandemic evolves into a 'new normal,' ongoing vigilance, improved understanding, and available vaccines and treatments equip us for future challenges. Priorities now include proactive pandemic strategies, early warnings, supported healthcare, public education, and addressing societal disparities for better health resilience and sustainability.

Carnosine/histidine-containing dipeptide supplementation improves depression and quality of life: systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Mental ill-health is a common and growing issue, affecting 1 in 8 individuals or 970 million people worldwide in 2019. Histidine-containing dipeptides (HCDs) have been suggested to mitigate some aspects of mental ill-health, but a quantitative synthesis of the evidence is lacking. Therefore, a systematic review and meta-analysis of randomized controlled trials was conducted. OBJECTIVE: To summarize the evidence on the effects of HCDs on mental health outcomes. DATA SOURCE: A systematic literature search was performed using electronic databases (Medline via Ovid, Embase via Ovid, Scopus, Google Scholar, and Cochrane) from inception to October, 2022. DATA EXTRACTION: Two authors independently extracted data using a structured extraction format. DATA ANALYSIS: Data analysis was performed using STATA version 17. Random-effects models were used, and heterogeneity was assessed using the I2 test. Quality appraisal was performed using the Cochrane risk-of-bias 2.0 tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. CONCLUSION: 5507 studies were identified, with 20 studies fulfilling the inclusion criteria. Eighteen studies comprising 776 participants were included in the meta-analysis. HCD supplementation (anserine/carnosine, l-carnosine, ß-alanine) caused a significant reduction in depression scores measured with the Becks Depression Inventory (-0.79; 95% CI: -1.24, -0.35; moderate certainty on GRADE) when compared with placebo. An increase in quality-of-life scores measured with the 36-item Short-Form survey (SF-36) (0.65; 95% CI: 0.00, 1.30) and low certainty on GRADE in HCDs (anserine/carnosine, l-carnosine, ß-alanine) when compared with placebo were found. However, the rest of the outcomes did not show a significant change between HCD supplementation and placebo. Although the number of studies included in the meta-analysis was modest, a significant mean reduction was observed in depression score as well as an increase in quality-of-life score for the HCD group when compared with placebo. Most of the studies included had small sample sizes with short follow-up periods and moderate to high risk of bias, highlighting the need for further, well-designed studies to improve the evidence base. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017075354.

Assessment of consumer demographics and food safety risks associated with ready-to-eat (RTE) homemade foods purchased online in the UAE.

In the UAE, female entrepreneurs, termed "Tajrat", sell a variety of homemade food products over online social media (OSM) platforms. Some of these food products are prepared and sold outside regulatory channels, with serious public health consequences. The study aimed to identify consumer demographics associated with purchasing of RTE, homemade food sold over in OSM platforms in the UAE and to assess the food quality by evaluating microbiological quality and fat percentage in RTE foods. A representative survey of the population of the UAE (n = 1303) was conducted, covering consumer demographics, frequency of purchase, and respondents' perception towards safety and nutritional value. 66 % of respondents were Emiratis, fifty percent of whom purchased RTE foods online. Moreover, 61 % of participants purchased from "Tajrat" via OSM as opposed to other sources. Convenience (47 %) and taste (41 %) were the main drivers for purchasing RTE homemade foods. Although 76 % of respondents have at least one member of their family considered vulnerable, the safety levels, quality, and nutritional value of such products did not carry the same significance. Microbiological analysis of 35 food samples purchased online from "Tajrat" was conducted. Listeria spp. was isolated from 22 % of the samples, 43 % showed positive Staphylococcus aureus, and 31 % of the samples had coliform bacteria. Total Fat Content of RTE homemade food samples ranged between 2.6 and 30 g/100 g which is considered high and can cause serious health issues if consumed frequently. Recommendations from this study will help policy makers and regulators in the UAE to develop and implement education strategies targeting homemade food handlers.

Infant feeding practices and risk of preschool obesity in AlAin, UAE: A cross-sectional study.

Early childhood obesity is serious public health problem, and poses a risk of obesity in later life. The study aimed to investigate whether infant feeding affects risk of overweight and obesity in preschool children in the United Arab Emirates (UAE). A cross-sectional study was carried out. Data was collected in a kindergarten in Al Ain, UAE. One hundred and fifty parents and preschool children aged 2 to 6 years participated in the study. Univariate and multivariate linear regression were used to investigate associations. A longer duration of breastfeeding and later introduction of complementary foods were associated with a lower BMI z-score in preschool children. Each month of any breastfeeding was associated with a lower BMI z-score in the unadjusted model (ß = -0.03; 95% CI -0.05, -0.01; p = 0.01), and each month increase in the age of introducing complementary foods was associated with a lower BMI z-score in the unadjusted model (ß = -0.43; 95% CI: -0.60 to-0.027; p<0.001). These associations remained after adjustment for potential confounding factors (age, sex, maternal BMI, maternal education level, mother's age, social class, father's BMI) for duration of breastfeedinig (ß = -0.02; 95% CI: -0.05 to 0.00; p<0.001) and age of complementary feeding (ß = -0.39; 95% CI: -0.57 to-0.21; p<0.001). Poor infant feeding practices (shorter duration of breastfeedinig and early introduction of complementary foods) were found to be associated with higher BMI in preschool children. Promoting appropriate proper infant feeding practices in line with recommendations could be one strategy to help prevent childhood obesity in the UAE.

Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Time-Restricted Fasting Improves Liver Steatosis in Non-Alcoholic Fatty Liver Disease-A Single Blinded Crossover Trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with visceral adiposity. We assessed the effectiveness of time-restricted fasting (TRF) for 16 h daily without calorie restrictions compared to standard care (SC; diet and lifestyle advice) in improving visceral adiposity and steatosis via controlled attenuation parameter (CAP). METHODS: In a prospective single-blind randomized controlled trial, 32 participants with NAFLD were randomly assigned to TRF or SC for 12 weeks. The secondary endpoints were changes in liver stiffness, anthropometry, blood pressure, and other metabolic factors. RESULTS: Twenty-eight participants completed the first arm of the study (TRF = 14, SC = 14), with 23 completing the crossover arm (TRF = 10, SC = 13). The baseline demographics were similar between the groups. Intermittent fasting caused a significant decrease in hepatic steatosis (p = 0.038), weight (p = 0.005), waist circumference (p = 0.001), and BMI (p = 0.005) compared to standard care. Intermittent fasting also resulted in additional within-group changes that were not seen in the standard care intervention. CONCLUSION: TRF offers superior improvements in patients with NAFLD, improving steatosis, weight, and waist circumference despite a lack of change in overall caloric intake. Time-restricted fasting should be considered as a primary weight loss intervention in the context of NAFLD. TRIAL REGISTRATION: ACTRN12613000935730.

Effects of carnosine and histidine-containing dipeptides on biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis.

CONTEXT: Carnosine and histidine-containing dipeptides (HCDs) are suggested to have anti-inflammatory and antioxidative benefits, but their effects on circulating adipokines and inflammatory and oxidative stress biomarkers remain unclear. OBJECTIVES: The aim of the present systematic review and meta-analysis was to determine the impact of HCD supplementation on inflammatory and oxidative stress biomarkers. DATA SOURCES: A systematic search was performed on Medline via Ovid, Scopus, Embase, ISI Web of Science, and the Cochrane Library databases from inception to 25 January 2023. DATA EXTRACTION: Using relevant key words, trials investigating the effects of carnosine/HCD supplementation on markers of inflammation and oxidative stress, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT) were identified. Meta-analyses were conducted using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). DATA ANALYSIS: A total of 9 trials comprising 350 participants were included in the present meta-analysis. Carnosine/HCD supplementation led to a significant reduction in CRP (WMD: -0.97 mg/L; 95% CI: -1.59, -0.36), TNF-α (WMD: -3.60 pg/mL; 95% CI: -7.03, -0.18), and MDA (WMD: -0.34 µmol/L; 95% CI: -0.56, -0.12) and an elevation in CAT (WMD: 4.48 U/mL; 95% CI: 2.43, 6.53) compared with placebo. In contrast, carnosine/HCD supplementation had no effect on IL-6, adiponectin, GSH, SOD, and TAC levels. CONCLUSION: Carnosine/HCD supplementation may reduce inflammatory and oxidative stress biomarkers, and potentially modulate the cardiometabolic risks associated with chronic low-grade inflammation and lipid peroxidation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017075354.

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data. Hence, we performed a 14-week double-blind randomized placebo-controlled trial to determine whether carnosine compared with placebo improves vascular and metabolic outcomes in individuals with prediabetes and T2DM. In total, 49 patients with prediabetes and T2DM with good glycemic control were randomly assigned either to receive 2 g/day carnosine or matching placebo. We evaluated endothelial dysfunction, arterial stiffness, lipid parameters, blood pressure, heart rate, hepatic and renal outcomes before and after the intervention. Carnosine supplementation had no effect on heart rate, peripheral and central blood pressure, endothelial function (logarithm of reactive hyperemia (LnRHI)), arterial stiffness (carotid femoral pulse wave velocity (CF PWV)), lipid parameters, liver fibroscan indicators, liver transient elastography, liver function tests, and renal outcomes compared to placebo. In conclusion, carnosine supplementation did not improve cardiovascular and cardiometabolic risk factors in adults with prediabetes and T2DM with good glycemic control. Therefore, it is improbable that carnosine supplementation would be a viable approach to mitigating the ASCVD risk in these populations. The trial was registered at clinicaltrials.gov (NCT02917928).

Differential Gene Expression of Checkpoint Markers and Cancer Markers in Mouse Models of Spontaneous Chronic Colitis.

The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.

Proximate composition and mineral content of spices increasingly employed in the Mediterranean diet.

The present study aimed to investigate the nutritional constituents of common market available spices in the United Arab Emirates. Seven commonly consumed spices namely, ginger (Zingiber officinale), cinnamon (Cinnamomum verum), black seed (Nigella sativa), fenugreek (Trigonella foenum-graecum), cardamom (Elettaria cardamomum), cloves (Syzygium aromaticum) and saffron (Crocus sativus) were obtained from local markets. Proximate analyses were performed according to AOAC procedures. Assessment of major (Ca, K, Mg, Na, P and S) and minor (Co, Cu, Fe, Mn and Zn) elements was conducted using inductively coupled plasma optical emission spectrometry (ICP-OES). Findings revealed varying macronutrient, micronutrient and mineral contents which are highly valuable for dietary purposes. The present study demonstrates that these edible spices could be used for nutritional support, due to their micro and macronutrient contents.

Circulating Osteoprogenitor Cells Have a Mixed Immune and Mesenchymal Progenitor Function in Humans.

BACKGROUND: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization of COP cells is still required to test and fully develop their use in clinical settings. METHODS: This study characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses. RESULTS: We demonstrate that COP cells have a distinct gene and protein expression pattern with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar expression pattern to BM-MSCs and ASCs. CONCLUSION: COP cells are a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.

Transcriptome analysis of the effects of polarized photobiomodulation on human dermal fibroblasts.

BACKGROUND: Photobiomodulation (PBM), the therapeutic use of light, is used to treat a myriad of conditions, including the management of acute and chronic wounds. Despite the presence of clinical evidence surrounding PBM, the fundamental mechanisms underpinning its efficacy remain unclear. There are several properties of light that can be altered in the application of PBM, of these, polarization-the filtering of light into specified plane(s)-is an attractive variable to investigate. AIMS: To evaluate transcriptomic changes in human dermal fibroblasts in response to polarized PBM. RESULTS: A total of 71 Differentially Expressed Genes (DEGs) are described. All DEGs were found in the polarized PBM group (P-PBM), relative to the control group (PC). Of the 71 DEGs, 10 genes were upregulated and 61 were downregulated. Most DEGs were either mitochondrial or extracellular matrix (ECM)-related. Gene Ontology (GO) analysis was then performed using the DEGs from the P-PBM vs. PC group. Within biological processes there were 95 terms found (p < 0.05); in the molecular function there were 18 terms found (p < 0.05); while in the cellular component there were 32 terms enriched (p < 0.05). A KEGG pathways analysis was performed for the DEGs found in the P-PBM vs. PC group. This revealed 21 significantly enriched pathways (p < 0.05). Finally, there were 24 significantly enriched reactome pathways when comparing the DEGs of the P-PBM vs. PC groups (p < 0.05). DISCUSSION AND CONCLUSIONS: The P-PBM DEGs were almost always down regulated compared to the comparator groups. This may be explained by the P-PBM treatment conditions decreasing the amount of cellular stress, hence causing a decreased mitochondria and ECM protective response. Alternatively, it could point to an alternate mechanism, outside the mitochondria, by which PBM exerts its effects. Additionally, PBM appears to have a more widespread effect on the mitochondria than previously thought, opening up many new avenues of investigation in the process.

Development of Methamphetamine Conjugated Vaccine through Hapten Design: In Vitro and In Vivo Characterization.

BACKGROUND: Methamphetamine (METH) substance-use disorder is an ever-growing global health issue with no effective treatment. Anti-METH vaccines are under investigation as an alternative to existing psychological interventions. This platform has made significant progress over past decades mainly in preclinical stages, and efforts to develop an anti-METH vaccine with a high antibody response are of utmost importance. METHODOLOGY: A novel conjugated anti-METH vaccine was developed using METH HCl as the starting material for the design of hapten, a peptide linker consisting of five lysines and five glycines, and finally immunogenic carrier mannan, which is novel to this platform. All the chemical reaction steps were confirmed by several analytical techniques, and the immunogenicity of the developed vaccine was investigated in a mouse model. RESULTS: Thin-layer chromatography and gas chromatography confirmed the reaction between METH and peptide linker. UV, NMR and color tests were used to confirm the presence of the aldehyde groups in oxidized mannan (OM). The final conjugated vaccine was confirmed by UV and LC-MS. The stability of mannan, the METH hapten, and the final vaccine was evaluated by UV and LC-MS and demonstrated satisfactory stability over 3 months in various storage conditions. Animal studies supported the immunogenicity of the novel vaccine. CONCLUSIONS: We successfully developed and characterized a novel METH vaccine in vitro and in vivo. The present study findings are encouraging and will form the basis of further exploration to assess its effectiveness to prevent METH addiction in preclinical models.

The impact of motivational interviewing on behavioural change and health outcomes in cancer patients and survivors. A systematic review and meta-analysis.

BACKGROUND: Cancer patients and survivors commonly have poorer health behaviours and subsequent outcomes, often as a result of negative impacts of diagnosis and treatment. Motivational interviewing is reported to be an effective psychological tool to produce a shift in one's behaviour resulting in improved outcomes. However, there is a lack of analyses investigating this tool's impact on healthy behaviours and health outcomes in cancer populations. OBJECTIVE: To investigate the effect of motivational interviewing on behaviours and health outcomes in cancer populations. METHODS: The studies were identified from four databases using variations of the terms "cancer" and "motivational interviewing". Randomised trials, non-randomised trials and quasi-experimental studies which contained control (or usual care) comparators were included. Risk of bias was assessed using the Cochrane Risk of Bias Version 5.1.0 and the Risk of Bias In Non-Randomised Studies of Interventions tools. The quality of evidence was assessed using the GRADE framework. Means difference and standardised mean differences and 95 % confidence intervals were used to report the pooled effects using a random effects model. RESULTS: Twenty-one studies were included in the review and 17 studies were included in the meta-analysis. A total of 1752 cancer patients and survivors received MI as an intervention (or part thereof). Quality of life, anxiety, depression, functional tasks (6-minute walk test), body mass index and body weight (BMI/BW), physical activity (PA), self-efficacy and fatigue were outcomes measured in the selected studies. Effects were seen in functional tasks, physical activity, BMI/BW, depression and self-efficacy. All of these outcomes were from studies that were classed as very low-quality evidence except for BMI/BW and PA, which were from moderate-quality evidence. CONCLUSION: Motivational interviewing had positive effects on functional tasks, PA, BMI/BW, depression and self-efficacy in people diagnosed with cancer. However, more higher-quality studies need to be conducted to further ascertain the effect of this intervention.

Liver-expressed antimicrobial peptide 2 is associated with improved pancreatic insulin secretion in adults with overweight and obesity.

AIMS: To examine association of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous ghrelin antagonist with anorexiant effects, to key cardiometabolic risk factors in people with overweight and obesity. METHODS: In this cross-sectional study, we sought to identify associations between LEAP2 levels and cardiometabolic risk factors, including body composition (dual X-ray absorptiometry), insulin and glucose metabolism (oral and intravenous glucose tolerance tests and hyperinsulinaemic-euglycaemic clamps), plasma lipids and inflammation markers (ELISA and multiplex assays). RESULTS: In 65 participants with overweight or obesity (63.1% male, mean age 31.3 ± 8.5 years), LEAP2 levels were associated with total body fat, but not with body mass index or waist-hip ratio in both univariable and age- and sex-adjusted models (P < 0.05). Higher LEAP2 level was also positively associated with higher insulin secretion in univariable (P = 0.047) and multivariable models adjusted for age, sex and body fat (P = 0.03), but not with fasting glucose levels (P ≥ 0.05). Higher LEAP2 levels were associated insulin resistance (P = 0.07) after adjustment for age and sex, but the association disappeared after an additional adjustment for body fat (P = 0.2). There was an inverse association between LEAP2 levels and nuclear factor kappa-B (NFκB) activity in the peripheral blood mononuclear cells in age-, sex- and body fat-adjusted models (P = 0.04). There were no associations with cardiovascular risk factors (lipids, blood pressure) or other inflammation markers. CONCLUSIONS: These results provide important insights into the association between LEAP2 and cardiometabolic health in a high-risk population of individuals with overweight and obesity. This is a first report of an association between LEAP2 and insulin secretion, insulin sensitivity and NFκB activity. LEAP2 may represent an important potential therapeutic target to promote insulin secretion in people with type 2 diabetes and obesity.

Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

The biological aging of mesenchymal stem cells is proposed to contribute to the development of a range of musculoskeletal and systemic diseases associated with older adults, such as osteoporosis, sarcopenia, and frailty. Despite this, little is understood about the specific mechanisms which drive this stem cell exhaustion, with most studies evaluating indirect effects of other aging changes, such as DNA damage, senescence, and inflammaging. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from males and females. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype associated with the pooled older stem cells, indicative of suppressed proliferation and differentiation; however, there was no consistent change in the proteome of the cells. Older MPCs had a distinct phenotype in both the transcriptome and proteome, again consistent with altered differentiation and proliferation, but also a pro-inflammatory immune shift in older adults. COP cells showed a strong transcriptomic shift to pro-inflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shift in physiologies associated with cell migration, adherence, and immune activation, but no consistent proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that likely contribute to a decline in tissue regeneration; however, contextual factors such as the microenvironment and general health status also have a strong role in this.

Cancer Immunotherapy: The Checkpoint between Chronic Colitis and Colorectal Cancer.

Inflammatory Bowel Disease (IBD) is a group of diseases that cause intestinal inflammation and lesions because of an abnormal immune response to host gut microflora. Corticosteroids, anti-inflammatories, and antibiotics are often used to reduce non-specific inflammation and relapse rates; however, such treatments are ineffective over time. Patients with chronic colitis are more susceptible to developing colorectal cancer, especially those with a longer duration of colitis. There is often a limit in using chemotherapy due to side effects, leading to reduced efficacy, leaving an urgent need to improve treatments and identify new therapeutic targets. Cancer immunotherapy has made significant advances in recent years and is mainly categorized as cancer vaccines, adoptive cellular immunotherapy, or immune checkpoint blockade therapies. Checkpoint markers are expressed on cancer cells to evade the immune system, and as a result checkpoint inhibitors have transformed cancer treatment in the last 5-10 years. Immune checkpoint inhibitors have produced long-lasting clinical responses in both single and combination therapies. Winnie mice are a viable model of spontaneous chronic colitis with immune responses like human IBD. Determining the expression levels of checkpoint markers in tissues from these mice will provide insights into disease initiation, progression, and cancer. Such information will lead to identification of novel checkpoint markers and the development of treatments with or without immune checkpoint inhibitors or vaccines to slow or stop disease progression.

Immunotherapies for the Treatment of Drug Addiction.

Substance use disorders (SUD) are a serious public health concern globally. Existing treatment platforms suffer from a lack of effectiveness. The development of immunotherapies against these substances of abuse for both prophylactic and therapeutic use has gained tremendous importance as an alternative and/or supplementary to existing therapies. Significant development has been made in this area over the last few decades. Herein, we highlight the vaccine and other biologics development strategies, preclinical, clinical updates along with challenges and future directions. Articles were searched in PubMed, ClinicalTrial.gov, and google electronic databases relevant to development, preclinical, clinical trials of nicotine, cocaine, methamphetamine, and opioid vaccines. Various new emerging vaccine development strategies for SUD were also identified through this search and discussed. A good number of vaccine candidates demonstrated promising results in preclinical and clinical phases and support the concept of developing a vaccine for SUD. However, there have been no ultimate success as yet, and there remain some challenges with a massive push to take more candidates to clinical trials for further evaluation to break the bottleneck.