The influence of occupational heat stress on serum inflammatory cytokines among traditional bakery workers in Iran.

Heat exposure exceeding the ISO7243:1989 standard limit can contribute to health problems among employees in a variety of workplaces. Ignoring heat standard requirements in hot working conditions such as bakeries results in physiologic and health problems, as well as an elevated risk of later illnesses. In this analytical case-control study, the serum levels of four inflammatory factors (interleukin-1 beta, interleukin-6, tumor necrosis factor-α, and C-reactive protein) were assessed using an enzyme-linked immunosorbent assay. 105 male artisan bakers (in four job classifications in bakeries and staff) were compared based on demographic characteristics and inflammatory factors. The findings of the study showed correlations between serum interleukin-1ß, interleukin-6, and C-reactive protein levels and thermal exposure in the occupational environment and employment type. Moreover, some differences in serum level of interleukin-1ß and job type were observed. Heat overexposure affected the increase of interleukin-1ß and C-reactive protein secretion. As a result of years of working in high-temperature conditions, inflammation can lead to subsequent diseases in workers. To protect their health from this occupational hazard, additional safeguards are needed. Our recommendations could also be applied to overly hot work environments that may cause heat stress in workers.

Tumor-educated platelets.

Beyond traditional roles in homeostasis and coagulation, growing evidence suggests that platelets also reflect malignant transformation in cancer. Platelets are present in the tumor microenvironment where they interact with cancer cells. This interaction results in direct and indirect "education" as evident by platelet alterations in adhesion molecules, glycoproteins, nucleic acids, proteins and various receptors. Subsequently, these tumor-educated platelets (TEPs) circulate throughout the body and play pivotal roles in promotion of tumor growth and dissemination. Accordingly, platelet status can be considered a unique blood-based biomarker that can potentially predict prognosis and therapeutic success. Recently, liquid biopsies including TEPs have received much attention as safe, minimally invasive and sensitive alternatives for patient management. Herein, we provide an overview of TEPs and explore their benefits and limitations in cancer.

Oleuropein reduces LPS-induced inflammation via stimulating M2 macrophage polarization.

Oleuropein (OLEU) is the most prevalent phenolic component in olive varieties, and it has been considered for its powerful antioxidant properties in therapeutic applications. OLEU has anti-inflammatory properties and performs this property by suppressing inflammatory cells' function and reducing oxidative stress caused by various factors. This study investigated the ability of OLEU to polarize LPS-stimulated murine macrophage (MQ) cell RAW 264.7 into M1/M2 macrophages. As a first step, the cytotoxicity effects of OLEU were evaluated on LPS-stimulated RAW 264.7 cells using the thiazolyl blue (MTT) colorimetric test. Then, cytokines production, gene expression (Real-Time PCR), and functions (Nitrite oxide assay and phagocytosis assay) of OLEU-treated LPS-stimulated RAW 264.7 cells were evaluated. Our findings demonstrated that OLEU could reduce nitrite oxide (NO) production in LPS-stimulated RAW 264.7 cells by downregulating the inducible nitric oxide synthase gene expression. Furthermore, OLEU therapy decreases the expression of M1-associated pro-inflammatory cytokines production (IL-12, IFN-γ, and TNF-α) and genes expression (iNOS, TNF-α) while increasing the M2-associated anti-inflammatory gene expression and cytokines production (IL-10, and TGF-ß). Based on the result, OLEU may be considered a potential therapeutic approach for inflammatory diseases due to its possible effects on oxidative stress-related factors, cytokine expression and production, and phagocytosis.

Recent insights into the roles of circular RNAs in human brain development and neurologic diseases.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs. They are single-stranded RNA transcripts characterized with a closed loop structure making them resistant to degrading enzymes. Recently, circRNAs have been suggested with regulatory roles in gene expression involved in controlling various biological processes. Notably, they have demonstrated abundance, dynamic expression, back-splicing events, and spatiotemporally regulation in the human brain. Accordingly, they are expected to be involved in brain functions and related diseases. Studies in animals and human brain have revealed differential expression of circRNAs in brain compartments. Interestingly, contributing roles of circRNAs in the regulation of central nervous system (CNS) development have been demonstrated in a number of studies. It has been proposed that circRNAs play role in substantial neurological functions like neurotransmitter-associated tasks, neural cells maturation, and functions of synapses. Furthermore, 3 main pathways have been identified in association with circRNAs's host genes including axon guidance, Wnt signaling, and transforming growth factor beta (TGF-ß) signaling pathways, which are known to be involved in substantial functions like migration and differentiation of neurons and specification of axons, and thus play role in brain development. In this review, we have an overview to the biogenesis, biological functions of circRNAs, and particularly their roles in human brain development and the pathogenesis of neurodegenerative diseases including Alzheimer's diseases, multiple sclerosis, Parkinson's disease and brain tumors.

Recent highlights in the immunomodulatory aspects of Treg cell-derived extracellular vesicles: special emphasis on autoimmune diseases and transplantation.

In order to maintain immunological tolerance to self and non-self antigens, one's T regulatory (Treg) cells play a critical role in the regulation of detrimental inflammation. Treg cells inhibit the immune system in a variety of ways, some of which are contact-dependent and the others are soluble factors. Extracellular vesicles (EVs) are mainly secretory membrane structures that play a pivotal role in intercellular communication in both the local and systemic environments, enabling the transport of proteins, lipids, and nucleic acids between immune and non-immune cells. A number of studies have shown that Treg-derived EVs are specially formulated intercellular exchanging devices capable of regulating immunological responses by producing a cell-free tolerogenic milieu. Some of the processes suggested include miRNA-induced gene shutdown and upmodulation, surface protein activity, and enzyme transfer. Instead of being influenced by external circumstances like Tregs, exosomes' cohesive structure allows them to transmit their charge intact across the blood-brain barrier and deliver it to the target cell with particular receptors. These properties have resulted in the use of Treg-derived EVs' immunomodulatory effects moving beyond laboratory research and into preclinical applications in animal models of a variety of inflammatory, autoimmune, and transplant rejection disorders. However, insufficient evidence has been produced to permit enrollment in human clinical studies. As such, we begin our research by introducing the most potent immunosuppressive elements discovered in Treg-derived EVs elucidating likely mechanisms of action in inhibiting immunological responses. Following that, we address recent research on the potential of suppressive EVs to regulate autoimmune inflammatory responses and improve tissue transplant survival.

Gene regulation by antisense transcription: A focus on neurological and cancer diseases.

Advances in high-throughput sequencing over the past decades have led to the identification of thousands of non-coding RNAs (ncRNAs), which play a major role in regulating gene expression. One emerging class of ncRNAs is the natural antisense transcripts (NATs), the RNA molecules transcribed from the opposite strand of a protein-coding gene locus. NATs are known to concordantly and discordantly regulate gene expression in both cis and trans manners at the transcriptional, post-transcriptional, translational, and epigenetic levels. Aberrant expression of NATs can therefore cause dysregulation in many biological pathways and has been observed in many genetic diseases. This review outlines the involvements and mechanisms of NATs in the pathogenesis of various diseases, with a special emphasis on neurodegenerative diseases and cancer. We also summarize recent findings on NAT knockdown and/or overexpression experiments and discuss the potential of NATs as promising targets for future gene therapies.

CiRS-7/CDR1as; An oncogenic circular RNA as a potential cancer biomarker.

Circular RNAs (circRNAs) as a new class of non-coding RNAs (ncRNAs) play role in gene regulation in multicellular organisms via various interactions with nucleic acids, proteins and particularly microRNAs. They have been found to be involved in a number of biological functions particularly in regulation of cell cycle, and extracellular interactions. Thus, dysregulation of circRNAs is found to be associated with several human diseases and especially numerous types of cancers. ciRS-7 is an example of circRNAs which have been studied in a number of human diseases like neurological diseases, diabetes mellitus, and importantly different malignancies. It has been found to regulate cell proliferation and malignant features in cancer cells. CiRS-7 is upregulated in several cancers and its overexpression promoted malignant phenotype of cancer cells via enhancing cell proliferation, migration, and invasion in vitro and in vivo. As a competing endogenous RNA (ceRNA), ciRS-7 is found to sponge miR-7 as the most common miRNA target in interaction together. Functional analyses show role of ciRS-7 in downregulation of miR-7 and involvement of a series of signaling pathways in turn through them it is believed that ciRS-7 regulates malignant behaviors of cancer cells. Clinical studies demonstrate upregulation of ciRS-7 in cancer tissues compared to their non-cancerous adjacent tissues, correlation with worse clinicopathological features in cancerous patients and an independent prognostic factor. In this review, we have an overview to the role of ciRS-7 in development and progression of cancer and also assess its potentials as a diagnostic and prognostic biomarker in human cancers.

Essential considerations during vaccine design against COVID-19 and review of pioneering vaccine candidate platforms.

The calamity of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), COVID-19, is still a global human tragedy. To date, no specific antiviral drug or therapy has been able to break the widespread of SARS-CoV2. It has been generally believed that stimulating protective immunity via universal vaccination is the individual strategy to manage this pandemic. Achieving an effective COVID-19 vaccine requires attention to the immunological and non-immunological standpoints mentioned in this article. Here, we try to introduce the considerable immunological aspects, potential antigen targets, appropriate adjuvants as well as key points in the various stages of COVID-19 vaccine development. Also, the principal features of the preclinical and clinical studies of pioneering COVID-19 vaccine candidates were pointed out by reviewing the available information. Finally, we discuss the key challenges in the successful design of the COVID-19 vaccine and address the most fundamental strengths and weaknesses of common vaccine platforms.

An overview of some potential immunotherapeutic options against COVID-19.

After the advent of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in the late 2019, the resulting severe and pernicious syndrome (COVID-19) immediately was deployed all around the world. To date, despite relentless efforts to control the disease by drug repurposing, there is no approved specific therapy for COVID-19. Given the role of innate and acquired immune components in the control and elimination of viral infections and inflammatory mutilations during SARS-CoV2 pathogenesis, immunotherapeutic strategies appear to be beneficent. Passive immunotherapies such as convalescent plasma, which has received much attention especially in severe cases, as well as suppressing inflammatory cytokines, interferon administration, inhibition of kinases and complement cascade, virus neutralization with key engineered products, cell-based therapies, immunomodulators and anti-inflammatory drugs are among the key immunotherapeutic approaches to deal with COVID-19, which is discussed in this review. Also, details of leading COVID-19 vaccine candidates as the most potent immunotherapy have been provided. However, despite salient improvements, there is still a lack of completely assured vaccines for universal application. Therefore, adopting proper immunotherapies according to the cytokine pattern and involved immune responses, alongside engineered biologics specially ACE2-Fc to curb SARS-CoV2 infection until achieving a tailored vaccine is probably the best strategy to better manage this pandemic. Therefore, gaining knowledge about the mechanism of action, potential targets, as well as the effectiveness of immune-based approaches to confront COVID-19 in the form of a well-ordered review study is highly momentous.

Extracellular vesicles (EVs): What we know of the mesmerizing roles of these tiny vesicles in hematological malignancies?

Cancer is a complex disease in which a bidirectional collaboration between malignant cells and surrounding microenvironment creates an appropriate platform which ultimately facilitates the progression of the disease. The discovery of extracellular vesicles (EVs) was a turning point in the modern era of cancer biology, as their importance in human malignancies has set the stage to widen research interest in the field of cell-to-cell communication. The implication in short- and long-distance interaction via horizontally transfer of cellular components, ranging from non-coding RNAs to functional proteins, as well as stimulating target cells receptors by the means of ligands anchored on their membrane endows these "tiny vesicles with giant impacts" with incredible potential to re-educate normal tissues, and thus, to re-shape the surrounding niche. In this review, we highlight the pathogenic roles of EVs in human cancers, with an extensive focus on the recent advances in hematological malignancies.

Effect of exercise on upper respiratory tract infection in elite runners.

BACKGROUND: Since it was assumed that exercise might be a risk factor for upper respiratory tract infection (URTI), the frequency, severity and duration of URTI were assessed in female elite runners compared with matched sedentary group. METHODS: A group of elite runners (N.=20) and one of sedentary subjects (N.=20) were selected and matched one by one for their age, nutritional state, their place of living and somewhat genetic factors. These groups were observed for any signs and symptoms of upper respiratory illnesses, during 2.5 cold months of the year. RESULTS: Although the mean number of the illnesses in elite athletes (1.0±0.8) was slightly lower than the control people (1.4±0.8); there was not any statistically significant difference between them (P>0.05). Furthermore, the mean days of disease (5.4±3.8 in elite athletes vs. 5.6±3.0 in control group) showed no significant statistical difference (P>0.05). Even though elite athletes showed no severe cases of the disease, no significant difference was observed between the two groups (P>0.05). CONCLUSIONS: Elite athletes are not at greater risk for URTI and this may be due to the suitable physiological status of athletes or attributed to" repeated bout effect" phenomenon.

Allium vegetables for possible future of cancer treatment.

Natural resources such as plants are an upright curing option in treating cancers and reducing the side effects of current therapeutic modalities. Allium genus vegetables are of the most interesting herbs in restricting cancers that includes garlic, onions, leeks, chives, and shallots. These plants have been exploited in folk medicine because of their beneficial health effects in improving numerous diseases. The phytochemical analysis of various Allium genus members showed that, to date, 16 species have proved potential anticancer properties due to the accumulation of various sulfur and organic compounds like S-allyl mercaptocysteine, quercetin, flavonoids, and ajoene. These compounds with various mechanisms such as hindering cell cycle, inhibiting signaling pathways, inducing apoptosis, and antioxidant activity interfere with diverse stages of formation, growth, differentiation, and metastasis of cancer cells. Similar to garlic and onion, other species have exhibited anticancer activities, so that active natural molecules extracted from them might serve as possible anticancer agents. Therefore, evaluating the main ingredients and studying their anticancer mechanisms are of great importance. In this review, we aim to summarize the available data on anticancer mechanisms of 16 species of Allium genus and their major compounds to assist further researches on the treatment and prevention of cancers.

Modulation of in vitro proliferation and cytokine secretion of human lymphocytes by Mentha longifolia extracts.

OBJECTIVE: Mentha longifolia L. Hudson has been used in folk medicine for various purposes especially for its anti-inflammatory effects. Lymphocytes play a central role in development of inflammation. In the present study, we investigated the immunomodulatory effects of different extracts of M. longifolia on human peripheral blood lymphocytes (PBLs), as main players in development of inflammation. MATERIALS AND METHODS: PBLs stimulated with phytohemagglutinin (PHA) were cultured in the presence of the plant extracts. The effects of the extracts on activation of cells were determined by BrdU assay. The viability of cells was examined by flow cytometry using propidium iodide staining. Also, IFN-γ (T helper 1, TH1) and IL-4 (TH2) secretion was measured by ELISA. RESULTS: Except for the water extract which had a weak inhibitory effect, treatment of cells with more than 1µg/ml of butanol, hexane, ethyl acetate and dichloromethane extracts resulted in strong inhibition of cells proliferation (IC50 4.6-9.9 µg/ml). Flow cytometry analysis showed that these extracts at ≤10µg/ml were non-cytotoxic. Dichloromethane and ethyl acetate extracts at 10 µg/ml decreased IFN-γ production in a dose-dependent manner from 919±91.1 pg/ml in PHA-only-treated cells to 568±22.6 pg/ml (in dichloromethane-treated cells) and 329±12.3 pg/ml (in ethyl acetate-treated cells) (p<0.001). At 10 µg/ml, the ethyl acetate extract increased IL-4 secretion compared to PHA-only-treated cells (p<0.05). The hexane extract decreased IFN-γ level but did not affectIL-4 production. CONCLUSION: Reduction of IFN-γ and augmentation of IL-4 secretion induced by the extracts suggested the potential of M. longifolia to inhibit TH1 inflammatory responses toward a TH2 dominant response.

Anticancer potential of Ferula hezarlalehzarica Y. Ajani fraction in Raji lymphoma cell line: induction of apoptosis, cell cycle arrest, and changes in mitochondrial membrane potential.

BACKGROUND: Cancer is a major cause of mortality. The present study evaluates the antitumor effects of Ferula hezarlalehzarica Y. Ajani fractions on various cancer cell lines, including the Raji Burkitt's lymphoma cells. METHODS: We evaluated the cytotoxic activity of various fractions of F. hezarlalehzarica against tumor cell lines by the MTT assay. Annexin V-PE/7-AAD and cell cycle analysis were assessed by flow cytometry. Expressions of genes associated with cell death and proliferation (Bax, Bcl-2, Fas, and c-Myc) were determined using real-time PCR. Alteration in mitochondrial membrane potential (MMP) was examined by JC-1 dye staining. RESULTS: The hexane fraction of F. hezarlalehzarica showed the highest degree of cytotoxicity against Raji cells (IC50 = 31.6 µg/ml). Flow cytometry analysis showed that 200 µg/ml of the fraction induced apoptosis in >96% of Raji cells after 24 h. In cell cycle analysis, at the same concentration, the percentage of apoptotic cells in the sub G1phase increased to 95.25 ± 1.76% at 48 h of treatment. The fraction induced cell cycle arrestat the G0/G1phase. Exposure to 100 µg/ml of the fraction after 48 h increased the percentage of G0/G1 cells (76.3 ± 6.08%) compared to the negative control (<50%). Treatment with75µg/ml of fraction reduced the expressions of Bcl-2 (0.23 ± 0.008-fold) and c-Myc (0.68 ± 0.07-fold) and increased Bax (1.75 ± 0.31-fold) and Fas (5.02 ± 0.74-fold; p < 0.01). We observed a decrease in MMP (≈0.4, p < 0.05) at ≥100 µg/ml and this effect remained almost unchanged until 48 h. CONCLUSIONS: The F. hezarlalehzarica hexane fraction induced apoptosis in Raji cells by changing the expression of apoptosis-related genes, cell cycle distribution, and MMP. These data suggested a potential effectiveness of F. hezarlalehzarica for inducing cell death in lymphoma cells. Graphical abstract ᅟ.