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"Zali, Mohammad Reza"
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Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors
The human gastrointestinal (GI) tract harbors gut microbiome, which plays a crucial role in preserving homeostasis at the intestinal host‐microbial interface. Conversely, specific gut microbiota may be altered during various pathological conditions and produce a number of toxic compounds and oncoproteins, in turn, to induce both inflammatory response and carcinogenesis. Recently, promising findings have been documented toward the implementation of certain intestinal microbiome in the next era of cancer biology and cancer immunotherapy. Notably, intestinal microbiota can cooperate with immune checkpoint inhibitors (ICIs) of its host, especially in enhancing the efficacy of programmed death 1 (PD‐1) protein and its ligand programmed death ligand 1 (PD‐L1) blockade therapy for cancer. Herein, we review the dual function of gut microbiota in triggering GI cancers, its association with host immunity and its beneficial functions in modulation of cancer immunotherapy responses. Furthermore, we consider the significance of gut microbiota as a potential biomarker for predicting the efficacy of cancer immunotherapy. Finally, we summarize the relevant limitations that affect the effectiveness and clinical applications of gut microbiome in response to immunotherapy. In this review, we discuss the dual role of gut microbiome in triggering GI cancers, its association with host immunity and its beneficial functions in modulation of cancer immunotherapy responses. Furthermore, we consider the significance of gut microbiota as a potential biomarker for predicting the response to immunotherapy.
Journal Article
Global Trend in Pancreatic Cancer Prevalence Rates Through 2040: An Illness‐Death Modeling Study
Background Despite remarkable progress in contemporary medical technology and enhanced survival outcomes for various cancer types, pancreatic cancer (PC) continues to stand out as a particularly deadly gastrointestinal malignancy. Given a persistent rise in both incidence and the corresponding mortality rates of PC globally, evaluations of PC burden by sex are of great importance. Here, we used the illness‐death multi‐state model (IDM) to forecast the prevalence of PC through the year 2040. Methods IDM was established based on obtainable data to predict the future prevalence of PC on global, regional, and national scales from 2019 to 2040. Analyses were also performed regarding sex and 95% confidence intervals (CIs) are presented for all estimates. Results The projected prevalence rate for 2040 is anticipated to be 6.093 ([95% CI 5.47–6.786] per 100,000) worldwide, indicating a significant increase of 31.45% since 1990, and a 12.29% increase since 2019. The estimated average annual increase since 2020 was 0.5%. Considering sex differences, females are expected to have a steeper slope in prevalence rate than males. Intriguingly, when considering the percentage changes between the periods of 2019–2040 and 1990–2019 for both sexes, females exhibited 29% and 11% increase relative to males (2.6‐fold greater increase). Conclusions By 2040, it is predicted that the prevalence of PC will increase globally, with women being at higher risk of developing the disease. Considering the percentage changes, regions with lower socioeconomic status are anticipated to face a greater risk of experiencing PC compared to other geographical areas.
Journal Article
Isolation and Functions of Extracellular Vesicles Derived from Parasites: The Promise of a New Era in Immunotherapy, Vaccination, and Diagnosis
Experimental and epidemiological evidence shows that parasites, particularly helminths, play a central role in balancing the host immunity. It was demonstrated that parasites can modulate immune responses via their excretory/secretory (ES) and some specific proteins. Extracellular vesicles (EVs) are nano-scale particles that are released from eukaryotic and prokaryotic cells. EVs in parasitological studies have been mostly employed for immunotherapy of autoimmune diseases, vaccination, and diagnosis. EVs can carry virulence factors and play a central role in the development of parasites in host cells. These molecules can manipulate the immune responses through transcriptional changes. Moreover, EVs derived from helminths modulate the immune system via provoking anti-inflammatory cytokines. On the other hand, EVs from parasite protozoa can induce efficient immunity, that makes them useful for probable next-generation vaccines. In addition, it seems that EVs from parasites may provide new diagnostic approaches for parasitic infections. In the current study, we reviewed isolation methods, functions, and applications of parasite's EVs in immunotherapy, vaccination, and diagnosis.
Journal Article
Endoscopic resection of polypoid solitary rectal ulcer: A novel first‐line therapeutic strategy using snare‐assisted mucosal and fibrosis resection
Objectives To propose a novel first‐line endoscopic therapy for treating polypoid lesions in solitary rectal ulcer syndrome (P‐SRUS), the rarest and most challenging subtype of SRUS, which encompasses various endoscopic findings including mucosal erythema, superficial or deep ulcers, and polypoid lesions. Methods A prospective, single‐arm study was conducted on 56 patients with histologically confirmed SRUS and broad‐based polypoid lesions in the rectum and anal canal. These patients were referred to the Department of Motility Disorders of the Lower Gastrointestinal Tract. The lesions were removed using snare‐assisted mucosal and fibrosis resection. Patients were monitored for clinical and endoscopic responses at 1, 3, 6, and 12 months post‐treatment. Results The study observed improvement in clinical symptoms, a complete endoscopic response, and the absence of late complications following endoscopic resection. Endoscopic evaluations revealed no recurrence of lesions in the follow‐up period. Conclusion Endoscopic resection using the snare‐assisted mucosal and fibrosis resection method appears to be an effective and safe treatment option for polypoid SRUS. (Clinical Trial Registration Number: IRCT20211101052935N2).
Journal Article
The neglected role of Enterobius vermicularis in appendicitis: A systematic review and meta-analysis
Although the main cause of appendicitis is unclear, infection with Enterobius vermicularis is suggested as a neglected risk factor. Since, there is no comprehensive analysis to estimate the prevalence of E. vermicularis in appendicitis; therefore, we conducted a global-scale systematic review and meta-analysis study to estimate the prevalence of E. vermicularis infection in appendicitis cases. PubMed, Scopus, Web of Science and Google Scholar databases were systematically searched for relevant studies published until 15 August 2019. Pooled prevalence of E. vermicularis infection was estimated using the random effects model. Data were classified based on the continents and countries. Moreover, subgroup analyses regarding the gender, the human development index (HDI), and income level of countries were also performed. Fifty-nine studies involving 103195 appendix tissue samples belonging to the individuals of appendicitis were included. The pooled prevalence of E. vermicularis infection was (4%, 95%CI, 2-6%), with the highest prevalence (8%, 95% CI: 0-36%) and lowest prevalence (2%, 95% CI: 1-4%) in Africa and Americas continents, respectively. With respect to countries, the lowest and highest prevalence rates were reported from Venezuela (<1%, 95% CI: 0-1%) and Nigeria (33%, 95% CI: 17-52%), respectively. Indeed, a higher prevalence was observed in females, as well as in countries with lower levels of income and HDI. Our findings indicate the relatively high burden of E. vermicularis infection in appendicitis cases. However, our findings suggest the great need for more epidemiological studies to depth understand overlaps between E. vermicularis infection and appendicitis in countries with lower HDI and income levels.
Journal Article
An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects
The incidence of gluten-related disorders (GRDs) continues to increase and its global prevalence is estimated at approximately 5% of the population. Celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) are the five major GRDs that present with a wide range of clinical manifestations. The diagnosis of GRDs can be challenging because the typical and atypical clinical manifestations of the GRDs overlap. In this review, the current definitions of gluten-related disorders, focusing on their clinical features, diagnostic and therapeutic approaches are presented. We concluded that GRDs are usually diagnosed using a combination of clinical features, serological tests, and histopathological findings. Treatment usually involves dietary modification.
Journal Article
Gender Inequality: Entrepreneurship Development in the MENA Region
Entrepreneurship is increasingly popular among policy makers worldwide to promote and achieve economic development and growth. However, entrepreneurship rates differ from one country to another, and particularly the number of women entrepreneurs is still significantly lower than the number of male entrepreneurs in many contexts. In the present paper, we critically assess how country measures of gender inequality shape men and women’s entrepreneurial intentions, which were shown in literature to be excellent predictors of the establishment of new ventures. We analyze the direct and moderating effects of gender inequality on important individual-level antecedents of entrepreneurial intention. The United Nations Development Program (UNDP) identified gender inequality as a key contributor to the loss of human development and declared “gender equality” as a sustainable development goal (SDG) in the UN 2030 agenda. Our research draws on the gender inequality index and GEM data from nine Middle Eastern and North African (MENA) countries. Our results show that a culture of inequality leads to limited entrepreneurial behavior by both men and women in a population.
Journal Article
Molecular epidemiology and genotype/subtype distribution of Blastocystis sp., Enterocytozoon bieneusi, and Encephalitozoon spp. in livestock: concern for emerging zoonotic infections
Intestinal parasitic infections have high prevalence rate in many regions especially in developing countries. The aim of this study was to determine the presence and genotype/subtype of some intestinal protozoa in livestock in Iran. Stool samples were collected from cattle, sheep, chickens, and horses. The presence of targeted parasites was evaluated using real-time PCR. Genotyping/subtyping of positive samples was characterized using sequencing of the ITS and barcoding region, respectively.
Blastocystis
sp., 27.7% (48/173) and
Enterocytozoon bieneusi
26.0% (45/173) were the most frequent protozoa followed by
Encephalitozoon
spp., 0.57% (1/173).
Cryptosporidium
spp. were not detected among samples.
Encephalitozoon
spp., was detected only in chickens 2.2% (1/45). A statistically correlation was seen between animals and the prevalence of targeted protozoa.
E. bieneusi
genotypes I (9/38; 23.68%), BEB6 (22/38; 57.89%), D (6/38; 15.79%), and horse1 (1/38; 2.63%) were detected among samples. A statistically significant correlation was seen between the genotypes and animals (
P
≤ 0.05).
Blastocystis
sp., ST1 (1/45; 2.22%), ST5 3/45; 6.66%), ST7 (1/45; 2.22%), ST10 (24/45; 53.33%), and ST14 (16/45; 35.55%) were characterized among samples. There was no significant correlation between certain subtypes and animals (
P
= 0.173). The presence of zoonotic potential genotypes of
E. bieneusi
in animals and zoonotic potential subtypes ST1 and ST7 among our samples provide a clue about the transmission dynamic of
E. bieneusi
and
Blastocystis
sp. between animals–animals and humans–animals.
Journal Article
Development and validation of a lipogenic genes panel for diagnosis and recurrence of colorectal cancer
Accumulated evidence indicates that the elevation of lipid metabolism is an essential step in colorectal cancer (CRC) development, and analysis of the key lipogenic mediators may lead to identifying the new clinically useful prognostic gene signatures.
The expression pattern of 61 lipogenic genes was assessed between CRC tumors and matched adjacent normal tissues in a training set (n = 257) with the Mann-Whitney U test. Cox's proportional hazards model and the Kaplan-Meier method were used to identifying a lipogenic-biomarkers signature associated with the prognosis of CRC. The biomarkers signature was then confirmed in two independent validation groups, including a set of 223 CRC samples and an additional set of 203 COAD profiles retrieving from the Cancer Genome Atlas (TCGA).
Five genes, including ACOT8, ACSL5, FASN, HMGCS2, and SCD1, were significantly enhanced in CRC tumors. Using the cutoff value 0.493, the samples were classified into high risk and low risk. The AUC of panel for discriminating of all, early (I-II stages), and advanced CRC (III-IV stages) were 0.8922, 0.8446, and 0.9162 (Training set), along with 0.8800, 0.8205, and 0.7351 (validation set I), and 0.9071, 0.8946, and 0.9107 (Validation set II), respectively. There was a reverse correlation between the high predicted point of panel and worse OS of CRC patients in training set (HR (95% CI): 0.1096 (0.07089-0.1694), P < 0.001), validation set I (HR (95% CI): 0.3350 (0.2116-0.5304), P < 0.001), and validation set II (HR (95% CI): 0.1568 (0.1090-0.2257), P < 0.001).
Our study showed that the panel of ACOT8/ACSL5/FASN/HMGBCS2/SCD1 genes had a better prognostic performance than validated clinical risk scales and is applicable for early detection of CRC and tumor recurrence.
Journal Article