Poor Sleep Quality and Its Influencing Factors Among Iranian Patients with Esophageal and Gastric Cancer.

Background: Sleep quality is a notable factor of well-being. It also may play a role in the development and progression of chronic diseases and cancers. Therefore, this study was performed to investigate poor sleep quality and its influencing factors among Iranian patients with esophageal and gastric cancer. Methods: In this cross-sectional study, a total of 312 Iranian adult patients who suffered from esophageal and gastric cancers were employed from a gastrointestinal cancer-based cohort study conducted in a referral hospital in Tehran between 2015 and 2018. Persian version of the Pittsburg Sleep Quality Index (PSQI) was used to measure poor sleep quality. Univariate and multiple logistic regression models were applied to determine the related factors to poor sleep quality. Results: Of the participants, 203 (65.06%) were men, and 75.96% had gastric cancer. The mean age was 63.13±12.10 years. The results demonstrated that more than 62% of the patients had poor sleep quality. 148 (62.44%) patients out of 237 patients with gastric cancer had poor-quality sleep. Also, 46 (64.38%) patients out of 237 patients with esophageal cancer had poor-quality sleep. Based on the results of multiple logistic regression models, marital status has a negative association with poor sleep quality (odds ratio [OR]=0.32, P=0.015). In addition, having chronic disease (OR=2.16; P=0.028) and wealth index (OR=3.11, P=0.013; OR=3.81, P=0.003; OR=3.29, P=0.009; OR=3.85, P=0.003 for rich, moderate, poor, and poorest subgroups, respectively) had a positive association with poor sleep quality. Conclusion: The findings showed that about two-thirds of the patients studied were poor sleepers. Also, it was observed that marital status, chronic disease, and wealth index were important factors associated with poor sleep quality.

The Long Noncoding RNA PANDAR as a Prognostic and Diagnostic Biomarker in Panceratic Cancer .

Pancreatic cancer (PC) is a lethal complication in the world, affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Most PC patients are confronted with locally metastatic or advanced diseases in the asymptomatic phase, and about 80% have late diagnosis with metastasis. Recently, long noncoding RNAs (lncRNAs) have drawn attention as a novel biological regulation layer. They take part in the regulation of mRNA and can be used as a prognostic factor or drug target. Based on their functions as regulators of PC initiation and progress, the lncRNAs can be categorized as tumor suppressors or oncogenic. They can be considered as a target for finding new biomarkers for prognosis, diagnosis, monitoring, and treating drug response in PC. Therefore, the present study summarizes the lncRNAs role in PC and the probable strategies to deal with their expression and controlling tumorigenesis and detection of the prognosis of PC.

The Circadian Clock as a Potential Biomarker and Therapeutic Target in Gastrointestinal Cancers.

The circadian clock consists of a hierarchical multi-oscillator network of intracellular and intercellular mechanisms throughout the body that contributes to anticipating metabolic activity and maintaining system homeostasis in response to environmental cues and intrinsic stimuli. Over the past few years, genetic variations of core clock genes have been associated with cancer risk in several epidemiological studies. A growing number of epidemiological research studies have demonstrated a direct correlation between the disturbance of circadian rhythms and the growth of tumors, indicating that shift workers are more susceptible to malignancies of the colon, prostate, ovarian, breast, lung, and liver. One of the most related cancers with circadian rhythm is Gastrointestinal (GI) cancer, which is a leading cause of cancer-related mortality nowadays. The aim of this review was to demonstrate the effect of the clock gene network on the growth of GI cancer, providing molecular targets for GI cancer treatment, possible prognostic biomarkers, and guidance for treatment choices.

Photodynamic Therapy as a Desirable Approach in the Treatment of Colorectal Cancer, with Special Focus on Photodynamic Nanotherapeutics in Immunotherapy.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide; however, there is not a convincing treatment for this disease. Limitations of conventional CRC therapies force scientists to develop novel treatment concepts for both primary care alongside adjuvant therapy. Photodynamic therapy (PDT) has been introduced as a promising therapeutic procedure for CRC mediated through theranostic principle in which special dyes, photosensitizers (PSs), are excited by near-infrared (NIR) and visible light. Recent studies showed that PDT has synergistic effects in combination with chemotherapy or immunotherapy in the treatment of CRC patients. Of note, nanoformulation of PS or immunotherapeutic agents could augment the PDT effectiveness. In this review, we summarize PDT application in CRC management with a special focus on the nanoparticles-based delivery system from the perspective of targeting deeper CRC and increased PDT efficiency, which could provide a desirable approach for clinical translation.

The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers.

Gastrointestinal (GI) cancer is one the most prevalent types of cancer. Despite current chemotherapy's success, patients with GI cancer continue to have a dismal outcome. The onset and progression of cancer are caused by alterations and the abnormal expression of several families of genes, like tumor-suppressor genes, oncogenes, and chemotherapy-resistant genes. The final purpose of tumor therapy is to inhibit cellular development by modifying mutations and editing the irregular expression of genes It has been reported that CDH1, TP53, KRAS, ARID1A, PTEN, and HLA-B are the commonly mutated genes in GI cancer. Gene editing has become one potential approach for cases with advanced or recurrent CRC, who are nonresponsive to conventional treatments and a variety of driver mutations along with progression cause GI progression. CRISPR/Cas9 technique is a reliable tool to edit the genome and understand the functions of mutations driving GI cancer development. CRISPR/Cas9 can be applied to genome therapy for GI cancers, particularly with reference to molecular-targeted medicines and suppressors. Moreover, it can be used as a therapeutic approach by knocking in/out multiple genes. The use of CRISPR/ Cas9 gene editing method for GI cancer therapy has therefore resulted in some improvements. There are several research works on the role of CRISPR/Cas9 in cancer treatment that are summarized in the following separate sections. Here, the use of CRISPR/Cas9-based genome editing in GI and the use of CRISPR/Cas9 is discussed in terms of Targeting Chemotherapy Resistance-related Genes like; KRAS, TP53, PTEN, and ARID1A.

Therapeutic Potential of Targeting Transforming Growth Factor-beta (TGF-ß) and Programmed Death-ligand 1 (PD-L1) in Pancreatic Cancer.

Pancreatic cancer (PC) is one the most lethal malignancies worldwide affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Transforming growth factor-beta (TGF-ß) is a multifunctional factor acting as both a tumor promoter in early cancer stages and a tumor suppressor in advanced disease. Programmed death-ligand 1 (PD-L1) is a ligand of programmed death-1 (PD-1), an immune checkpoint receptor, allowing tumor cells to avoid elimination by immune cells. Recently, targeting the TGF-ß signaling and PD-L1 pathways has emerged as a strategy for cancer therapy. In this review, we have summarized the current knowledge regarding these pathways and their contribution to tumor development with a focus on PC. Moreover, we have reviewed the role of TGF-ß and PD-L1 blockade in the treatment of various cancer types, including PC, and discussed the clinical trials evaluating TGF-ß and PD-L1 antagonists in PC patients.

Natriuretic Peptides in Gastrointestinal Cancer: Biomarkers and Potential Therapeutic Targets.

Gastrointestinal (GI) cancers are an important health problem globally. Natriuretic peptides are hormones that have a crucial role in human physiology. There are a variety of treatments for GI cancer, but conventional therapies have side effects and low efficacy. Studies have demonstrated that natriuretic peptides are therapeutic in different cancer types. Natriuretic peptides are best known for their involvement in regulating blood pressure and blood volume. The anti-tumor effect exerted by natriuretic peptides is via their inhibitory effects on DNA synthesis and by their effects on apoptosis. The anti-proliferative role of natriuretic peptides has been shown in human breast cancer, prostate, colon, pancreatic, lung, ovarian, and other tumors. The roles of natriuretic peptides in these cancers are diverse and not well understood. Therefore, we have reviewed the recent literature on natriuretic peptides in GI cancers as a common malignancy in adults to assess the pathways that NPs are involved in the progression of GI cancers and its effect on the prevention or treatment of GI cancers.

The potential therapeutic applications of CRISPR/Cas9 in colorectal cancer.

The application of the CRISPR-associated nuclease 9 (Cas9) system in tumor studies has led to the discovery of several new treatment strategies for colorectal cancer (CRC), including the recognition of novel target genes, the construction of animal mass models, and the identification of genes related to chemotherapy resistance. CRISPR/Cas9 can be applied to genome therapy for CRC, particularly regarding molecular-targeted medicines and suppressors. This review summarizes some aspects of using CRISPR/Cas9 in treating CRC. Further in-depth and systematic research is required to fully realize the potential of CRISPR/Cas9 in CRC treatment and integrate it into clinical practice.

Household Food Insecurity and Associated Factors among Iranian Patients with Esophageal and Gastric Cancers.

Background: Household food insecurity (HFI) which has still been one of the major global public health issues is related to adverse health outcomes in individuals. Therefore, this study aimed to determine the prevalence of HFI and its associated factors in Iranian patients with esophageal and gastric cancers. Methods: The data of this cross-sectional study was obtained from 315 patients with esophageal and gastric cancers who were selected from a gastrointestinal cancer-based cohort study conducted in Firoozgar hospital, in Tehran. Food insecurity (FI) was measured using the Iranian version of the HFI questionnaire that was completed by a trained interviewer. The multivariable logistic regression model was used to determine the independent association of each factor with HFI. A P value lower than 0.05 was considered statistically significant. Results: The mean±SD of participants' age was 63.2±12.6 years and 65.4% were men. Most of the patients (75.8%) suffered from gastric cancer and 24.2% from esophageal cancer. The overall prevalence of FI among participants' households was 35.2%. There was an independent significant association between wealth index (WI) and HFI after the use of the multivariable logistic regression model, in such a way that the odds of FI in the poorest, poor, moderate, and rich patients' households were respectively, 6.41, 5.05, 2.74 and 2.04 times higher compared with the richest households. Conclusion: More than a third of participants' households struggled with FI, which was found to have a higher prevalence in loweconomic households. Therefore, health policymakers should intervene in food-insecure households by developing, establishing, and implementing strategies and control programs to improve affordable food access.

Remodeling of the Gut Microbiota in Colorectal Cancer and its Association with Obesity.

The considerable burden of colorectal cancer and the increasing prevalence in young adults emphasizes the necessity of understanding its underlying mechanisms and risk factors as well as providing more effective treatments. There is growing evidence of a positive relationship between obesity and colorectal cancer. Furthermore, the prominent role of gut microbiota dysbiosis in colorectal carcinogenesis is becoming more evident. Sequencing studies demonstrate an altered composition and ecology of intestinal microorganisms in both colorectal cancer and obese patients and have pinpointed some specific bacteria as the key role players. The purpose of this review is to provide a general outlook of how gut microbiota may impact the initiation and promotion of colorectal cancer and describes probable links between gut microbiota and obesity. We also provide evidence about targeting the microbiota as an intervention strategy for both ameliorating the risk of cancer and augmenting the therapy efficacy.

Growth-hormone-releasing Hormone as a Prognostic Biomarker and Therapeutic Target in Gastrointestinal Cancer.

Gastrointestinal cancers are prevalent cancers in the world with a poor prognosis, causing about one-half of all cancer deaths in the world. Unfortunately, there is no effective treatment for GI cancers. GHRH and GHRH receptors (GHRH-R) are expressed in various tumoral tissues and cell lines. The inhibition of GHRH-R is a new area of research because it provides a possible means of treating several types of cancer. Recent publications have reported GHRH and GHRH-R expressions in breast, pancreatic, prostate, colon, gastric, ovarian, and lung cancers, along with promising data about the use of GHRH antagonists in the treatment of different cancers. This review aims to summarize the recent studies on the relationship between GHRH and GI cancers and assess whether this hormone can be our target for therapy or used as a prognostic marker for GI cancers.

Assessment of Probiotics Mixture on Memory Function, Inflammation Markers, and Oxidative Stress in an Alzheimer's Disease Model of Rats.

Background: The most important cause of neurodegeneration in Alzheimer's disease (AD) is associated with inflammation and oxidative stress. Probiotics are microorganisms that are believed to be beneficial to human and animals. Probiotics reduce oxidative stress and inflammation in some cases. Therefore, this study determined the effects of probiotics mixture on the biomarkers of oxidative stress and inflammation in an AD model of rats. Methods: In this study, 50 rats were allocated to five groups, namely control, sham, and AD groups with Aß1-40 intra-hippocampal injection, as well as AD + rivastigmine and AD + probiotics groups with Aß1-40 intra-hippocampal injection and 2 ml (1010 CFU) of probiotics (Lactobacillus reuteri, Lactobacillus rhamnosus, and Bifidobacterium infantis) orally once a day for 10 weeks. MWM was used to assess memory and learning. To detect Aß plaque, Congo red staining was used. Oxidative stress was monitored by measuring the MDA level and SOD activity, and to assess inflammation markers (IL-1ß and TNF-α) in the hippocampus, ELISA method was employed.. Results: Spatial memory improved significantly in treatment group as measured by MWM. Probiotics administration reduced Aß plaques in AD rats. MDA decreased and SOD increased in the treatment group. Besides, probiotics reduced IL-1ß and TNF-α as inflammation markers in the AD model of rats. Conclusion: Our data revealed that probiotics are helpful in attenuating inflammation and oxidative stress in AD.

Hypoxic-conditioned medium from adipose tissue mesenchymal stem cells improved neuroinflammation through alternation of toll like receptor (TLR) 2 and TLR4 expression in model of Alzheimer's disease rats.

Microglia have a pivotal role to initiate immune responses in AD brains through toll-like receptors and induce neuroinflammation. Adipose tissue mesenchymal stem cells (ATSCs) secret many neurotrophic and anti-inflammatory factors called conditioned medium (CM). Many studies have demonstrated that CM of mesenchymal stem cells facilitate regeneration and attenuates inflammation in many disorders. To this purpose, the effect of ATSCs-conditioned medium (ATSC-CM) on brain inflammation and the role of toll-like receptors were investigated in this study. Seventy-two rats were randomly divided into 6 groups: control, sham, sham+ATSC-CM: 200µl ATSC-CM once a day intraperitoneally for 8 days, AD group injected the Aß1-40 intra-hippocampal, AD+ASC-CM, which was injected Aß1-40 intra-hippocampal and 200µl ATSC-CM once a day intraperitoneally for 8 days and AD+ rivastigmine: was injected Aß1-40 intra-hippocampal and received rivastigmine (0.6 mg/kg) orally once a day for 2 weeks. Memory and learning were measured by Morris water maze and novel object recognition tests. For detection of beta-amyloid plaque, Congo red staining was used, and neuronal survival was assessed by Nissl staining. Expression of TLR2 and TLR4 was measured by real-time PCR, and finally, to assess inflammation markers (IL-1ß and TNF-α) in the hippocampus, ELISA kits were used. In treatment group spatial and recognition memory significantly was improved. ATSC-CM administration decreased beta amyloid plaques and enhanced neuronal survival in AD brain rats. In addition, TLR2 and TLR4 expression decreased in treatment group. Results also showed that ATSC-CM reduced IL-1ß and TNF-α as inflammation markers. ATSC-CM improved memory deficit, decreased beta amyloids formation, increased neuron survival, and attenuated inflammation by reducing the expression of TLRs.