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Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease-19 (COVID-19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID-19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID-19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll-like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID-19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID-19 disease severity. Understanding host immune gene variations associated with the SARS-COV-2 infection opens insights to control the pathophysiology of emerging viral infections.
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COVID-19 , Citocinas , Receptores de Citocinas , Receptores Toll-Like , COVID-19/genética , COVID-19/fisiopatología , Síndrome de Liberación de Citoquinas/genética , Citocinas/genética , Humanos , Receptores de Citocinas/genética , SARS-CoV-2 , Receptores Toll-Like/genéticaRESUMEN
Owing to non-responsiveness of a high number of patients to the common melanoma therapies, seeking novel approaches seem as an unmet requirement. Chimeric antigen receptor (CAR) T cells were initially employed against recurrent or refractory B cell malignancies. However, advanced stages or pretreated patients have insufficient T cells (lymphopenia) amount for collection and clinical application. Additionally, this process is time-consuming and logistically cumbersome. Another limitation of this approach is toxicity and cytokine release syndrome (CRS) progress and neurotoxicity syndrome (NS). Natural killer (NK) cells are a versatile component of the innate immunity and have several advantages over T cells in the application for therapies such as availability, unique biological features, safety profile, cost effectiveness and higher tissue residence. Additionally, CAR NK cells do not develop Graft-versus-host disease (GvHD) and are independent of host HLA genotype. Notably, the NK cells number and activity is affected in the tumor microenvironment (TME), paving the way for developing novel approaches by enhancing their maturation and functionality. The CAR NK cells short lifespan is a double edge sword declining toxicity and reducing their persistence. Bispecific and Trispecific Killer Cell Engagers (BiKE and Trike, respectively) are emerging and promising immunotherapies for efficient antibody dependent cell cytotoxicity (ADCC). CAR NK cells have some limitations in terms of expanding and transducing NK cells from donors to achieve clinical response. Clinical trials are in scarcity regarding the CAR NK cell-based cancer therapies. The CAR NK cells short life span following irradiation before infusion limits their efficiency inhibiting their in vivo expansion. The CAR NK cells efficacy enhancement in terms of lifespan TME preparation and stability is a goal for melanoma treatment. Combination therapies using CAR NK cells and chemotherapy can also overcome therapy limitations.
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Melanoma , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Células Asesinas Naturales , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia , Melanoma/terapia , Melanoma/etiología , Microambiente TumoralRESUMEN
Chimeric antigen receptor T (CAR-T) cell therapy procedure includes taking personal T cells and processing or genetic engineering using specific antigens and in vitro expanding and eventually infusing into the patient's body to unleash immune responses. Adoptive cell therapy (ACT) includes lymphocytes taking, in vitro selection and expansion and processing for stimulation or activation and infusion into the patient's body. Immune checkpoint inhibitors (ICIs), ACT and CAR-T cell therapies have demonstrated acceptable results. However, rare CAR-T cells tissue infiltration, off-target toxicity and resistance development include main disadvantages of CAR-T cell based therapy. Selection of suitable target antigens and novel engineered immune cells are warranted in future studies using "surfaceome" analysis. Employment of cytokines (IL-2, IL-7) for T cells activation has been also associated with specific anti-melanoma function which overcome telomeres shortening and further T cells differentiation. In resistant cases, rapidly accelerated fibrosarcoma B-type and mitogen-activated extracellular signal-regulated kinase inhibitors have been mostly applied. The aim of this study was evaluation of CAR-T cell and adoptive cell therapies efficiency for the treatment of melanoma.
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Melanoma , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Receptores de Antígenos de Linfocitos T/genética , Inmunoterapia Adoptiva/métodos , Melanoma/terapia , Linfocitos T , InmunoterapiaRESUMEN
BACKGROUND: Breast cancer is the most frequent cancer among women. Despite the effectiveness of Doxorubicin (DOX) as a chemotherapeutic for the treatment of breast cancer, the therapy-resistance remains unsolvable. Apigenin is a natural dietary flavonoid with potential anticancer activities. Our study's intention was to evaluate the effect of Apigenin on DOX resistance in MCF-7 cells. METHODS: DOX-resistant MCF-7 cell line (MCF-7R) was developed by treating MCF-7 cells with increasing concentrations of DOX (0-100 µM). The viability of cell lines was assayed using MTT method. Quantitative polymerase chain reaction method was performed to measure multidrug-resistance 1 (MDR1) gene expression level. The expression of MDR1, Janus kinase 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3) proteins were determined by western blotting. RESULTS: MCF-7R cell line showed resistance to DOX in comparison to MCF-7 cells. Apigenin had a significant effect on the reduction of viability of both MCF-7 and MCF-7R cell lines. However, DOX-resistance in the MCF-7 cell line was considerably decreased due to the co-treatment of MCF-7R cells with Apigenin. This natural compound also downregulated the expression of MDR1 at mRNA and protein levels both in resistant and non-resistant cells. Apigenin significantly prohibited the phosphorylation and activation of JAK2 and STAT3 proteins both in MCF-7 and MCF-7R cell lines. CONCLUSIONS: The present results suggested, for the first time, Apigenin as an ideal therapeutic for ameliorating DOX resistance in breast cancer. These data also proposed a novel mechanism for the anti-resistance activity of Apigenin by regulating the JAK2/STAT3/MDR1 axis.
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Apigenina , Neoplasias de la Mama , Apigenina/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Células MCF-7 , Transducción de SeñalRESUMEN
Increasing data have shown the significance of various miRNAs in malignancy. In this regard, parallel to its biological role in normal tissues, miRNA-128 (miR-128) has been found to play an essential immunomodulatory function in the process of cancer initiation and development. The occurrence of the aberrant expression of miR-128 in tumors and the unique properties of miRNAs raise the prospect of their use as biomarkers and the next generation of molecular anticancer therapies. The function of miR-128 in malignancies such as breast, prostate, colorectal, gastric, pancreatic, esophageal, cervical, ovarian and bladder cancers and hepatocellular carcinoma is discussed in this review. Finally, the effect of exosomal miR-128 on cancer resistance to therapeutics and cancer immunotherapy in certain malignancies is highlighted.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Neoplasias Urogenitales , Masculino , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Próstata/metabolismoRESUMEN
OBJECTIVE: The aim: To determine the distribution of Candida spp. within different age groups and contraceptive methods in women with vulvovaginitis, as well as the susceptibility of Candida spp. to commonly used antifungals. PATIENTS AND METHODS: Materials and methods: High vaginal swabs were taken from 98 women aged 18 to 50 with vulvovaginitis who used contraceptives and attended the Women and Children Hospital in Al-Diwaniyah; after diagnosis of Candida species, the sensitivity of Candida spp. to some antifungals was studied. RESULTS: Results: The results showed (43/98) women (43.87%) used IUD, (15/98) women (15.30%) used birth control pills, (7/98) women (7.14%) used an injection of contraceptive, (5/98) women (5.10%) used contraceptive suppositories, and (28/98) women (28.57%) did not use any contraceptives. Candida spp. was found in (48/83) specimens (57.831%) from women who used contraceptives and only (11/28) specimens (39.285%) from women who did not use contraceptives. Only (59/98) vaginal specimens tested positive for vaginal candidiasis, (28/59) isolates (47.457%) for C. albicans, then (16/59) isolates for C. glabrata (27.118%), (9/59) isolates (15.254%) for C. tropicalis and (6/59) isolates (10.169%) for C. krusei. Nystatin was the best treatment for all Candida spp. under study, and the MIC was 6.25, and the MFC was 50 for all antifungals and Candida species under study. CONCLUSION: Conclusions: C. albicans was the most prevalent cause of vulvovaginal candidiasis, while C. glabrata was the most common non-albicans species in women aged 26 to 35; using an IUD was associated with an increased infection of vulvovaginal candidiasis, and nystatin was the most effective treatment.
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Candidiasis Vulvovaginal , Vulvovaginitis , Antifúngicos , Candida , Candida albicans , Niño , Anticoncepción , Anticonceptivos , Femenino , Humanos , Nistatina , Pichia , SupositoriosRESUMEN
In women, breast cancer (BC) is the second most frequently diagnosed cancer and the leading cause of cancer death. Mesenchymal stem cells (MSCs) are a subgroup of heterogeneous non-hematopoietic fibroblast-like cells that have the ability to differentiate into multiple cell types. Recent studies stated that MSCs can migrate into the tumor sites and exert various effect on tumor growth and development. Multiple researches have demonstrated that MSCs can favor tumor growth, while other groups have indicated that MSCs inhibit tumor development. Emerging evidences showed exosomes (Exo) as a new mechanism of cell communication which are essential for the crosstalk between MSCs and BC cells. MSC-derived Exo (MSCs-Exo) could mimic the numerous effects on the proliferation, metastasis, and drug response through carrying a wide scale of molecules, such as proteins, lipids, messenger RNAs, and microRNAs to BC cells. Consequently, in the present literature, we summarized the biogenesis and cargo of Exo and reviewed the role of MSCs-Exo in development of BC.
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Neoplasias de la Mama , Exosomas , Células Madre Mesenquimatosas , MicroARNs , Humanos , Femenino , Neoplasias de la Mama/patología , Exosomas/metabolismo , MicroARNs/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
In spite of progresses in the therapy of different malignancies, melanoma still remains as one of lethal types of skin tumor. Melanoma is almost easily treatable by surgery alone with higher overall survival rates when it is diagnosed at early stages. However, survival rates are decreased remarkably upon survival if the tumor is progressed to advanced metastatic stages. Immunotherapeutics have been prosperous in the development of anti-tumor responses in patients with melanoma through promotion of the tumor-specific effector T cells in vivo; nonetheless, suitable clinical outcomes have not been satisfactory. One of the underlying causes of the unfavorable clinical outcomes might stem from adverse effects of regulatory T (Treg) cell, which is a prominent mechanism of tumor cells to escape from tumor-specific immune responses. Evidence shows that a poor prognosis and low survival rate in patients with melanoma can be attributed to a higher Treg cell number and function in these subjects. As a result, to promote melanoma-specific anti-tumor responses, depletion of Treg cells appears to be a promising approach; even though the clinical efficacy of different approaches to attain appropriate Treg cell depletion has been inconsistent. Here in this review, the main purpose is to assess the role of Treg cells in the initiation and perpetuation of melanoma and to discuss effective strategies for Treg cell modulation with the aim of melanoma therapy.
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Melanoma , Neoplasias Cutáneas , Humanos , Linfocitos T Reguladores , Resultado del Tratamiento , InmunidadRESUMEN
PURPOSE: Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate cisplatin-induced ototoxicity. In the present study, we reviewed the protective potentials of alpha-lipoic acid against the cisplatin-mediated ototoxic adverse effects. METHODS: Based on the PRISMA guideline, we performed a systematic search for the identification of all relevant studies in various electronic databases up to June 2022. According to the inclusion and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally included in the present study. RESULTS: The findings of in-vitro experiments showed that cisplatin treatment signiï¬cantly reduced the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid co-administration protected the cells against the reduction of cell viability induced by cisplatin treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin treatment could significantly induce the biochemical and histopathological alterations in inner ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical and histological changes. CONCLUSION: The findings of audiometry, biochemical parameters, and histological evaluation showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different mechanisms of anti-oxidant, anti-apoptotic, anti-inï¬ammatory activities, and regulation of cell cycle progression.
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BACKGROUND: Previous studies have shown that physical appearance perfectionism could play an important role in social physique anxiety; however, the moderating role of body compassion has not been studied. The current study aims to explore the moderating role of body compassion in the relationship between physical appearance perfectionism and social physique anxiety in undergraduate students. METHODS: A sample of 418 undergraduates (n = 418; 217 female and 201 males) from three universities in Tehran, Iran completed online questionnaires measuring physical appearance perfectionism, body compassion and social physique anxiety. RESULTS: The results of structural equation modeling showed that physical appearance perfectionism (ß = 0.68, p < 0.001) positively predicted the social physique anxiety and body compassion negatively predicted (ß = - .56, p < 0.001) the social physique anxiety in undergraduate students. A multi-group analysis showed that body compassion acted as a moderator between physical appearance perfectionism and social physique anxiety. CONCLUSIONS: The results suggested that individuals with greater levels of physical appearance perfectionism are more likely to experience social physique anxiety. Also, the results suggested that individuals who were at a high level of the body-compassion group experienced lower levels of social physical anxiety if they also had high levels of physical appearance perfectionism. Therefore, body-compassion acted as a protective role in the relationship between physical appearance perfectionism and social physique anxiety.
Anxiety over one's physical appearance in social situations is known as social physique anxiety. One of the variables that plays an important role social physique anxiety is physical appearance perfectionism. General perfectionism, body dissatisfaction, the symptoms of eating disorders and muscle dysmorphia and obsessive exercise are all linked to physical appearance perfectionism. The results of the current study showed individuals with high levels of physical appearance perfectionism are more likely to experience social physique anxiety. In the current study, we tested the moderating role of self-compassion in the relationship between physical appearance perfectionism and social physique anxiety. Body compassion is characterized by diffusion, common humanity, and acceptance of one's own body as opposed to being judgmental, critical, isolated, and over-identifying with unpleasant experiences and emotions. The findings showed in the group with high body- compassion, the relationship between physical appearance perfectionism and social physique anxiety was not significant, which means that body-compassion played a buffering role in this relationship.
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Nowadays, emerging data demonstrate that the toll-like receptor (TLR) signaling pathway plays an important role in the progression of inflammatory atherosclerosis. Indeed, dysregulated TLR signaling pathway could be a cornerstone of inflammation and atherosclerosis, which contributes to the development of cardiovascular diseases. It is interesting to note that this pathway is heavily controlled by several mechanisms, such as epigenetic factors in which the role of non-coding RNAs (ncRNAs), particularly microRNAs and long noncoding RNAs as well as circular RNAs in the pathogenesis of atherosclerosis has been well studied. Recent years have seen a significant surge in the amount of research exploring the interplay between ncRNAs and TLR signaling pathway downstream targets in the development of atherosclerosis; however, there is still considerable room for improvement in this field. The current study was designed to review underlying mechanisms of TLR signaling pathway and ncRNA interactions to shed light on therapeutic implications in patients with atherosclerosis.
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BACKGROUND: However, broad adoption of herbal remedies for giardiasis is at present hampered by uncertain findings of investigation not always sufficiently powered. This study was aimed at systematically reviewing the existing literature in herbal medicines to treat giardiasis. METHODS: This review was carried out 06- PRISMA guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. The search was performed in five databases which are Scopus, PubMed, Web of Science, EMBASE, and Google Scholar without time limitation for all published articles (in vitro, in vivo, and clinical studies). The searched words and terms were: "Giardia", "giardiasis", "extract", "essential oil", "herbal medicines", "anti-Giardia", "In vitro", "In vivo", "clinical trial" etc. RESULTS: Out of 1585 papers, 40 papers including 28 in vitro (70.0%), 7 in vivo (17.5%), 2 in vitro/ in vivo (5.0%), and 3 clinical trials (7.5%) up to 2020, met the inclusion criteria for discussion in this systematic review. The most widely used medicinal plants against Giardia infection belong to the family Lamiaceae (30.0%) followed by Asteraceae (13.5%), Apiaceae (10.5%). The most common parts used in the studies were aerial parts (45.0%) followed by leaves (27.4%) and seeds (7.5%). The aqueous extract (30.0%), essential oil (25.4%) and hydroalcholic and methanolic (10.5%) were considered as the desired approaches of herbal extraction, respectively. CONCLUSION: The current review showed that the plant-based anti-Giardia agents are very promising as an alternative and complementary resource for treating giardiasis since had low significant toxicity. However, more studies are required to elucidate this conclusion, especially in clinical systems.
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BACKGROUND: Today, a suitable vaccine has not yet been discovered to prevent Toxoplasma gondii infection. Therefore, prophylaxis can be suggested as the preferred approach to prevent toxoplasmosis. This study aims to evaluate the prophylactic effects of synthesized zinc nanoparticles (ZnNPs) using Lavandula angustifolia Vera., by microwave method on chronic toxoplasmosis in mice. METHODS: BALB/c Mice orally administrated with ZnNPs the doses of 32.5, 75, 150 mg/kg/day for two weeks. On the 15th day, the mice were intraperitoneally infected with the Tehran strain of T. gondii (25 tissue cysts). The mean diameter and the numbers of brain tissue cysts, as well as the mRNA levels of inducible nitric oxide synthesize (iNOs), and interferon-gamma (IFN-γ) in mice of each experimental group were evaluated. RESULTS: The synthesized ZnNPs represent a spherical form with a size ranging from 30 to 80 nm. The results revealed that oral administration of Zn NPs at the doses of 32.5 (p < 0.001) and 75 mg/kg/day (p < 0.001) for 14 days significantly reduced the mean number and diameter of the brain tissue cysts in tested mice. No T. gondii tissue cyst was observed after oral administration of Zn NPs at the doses of 150 mg/kg. Based on the results of Real-time PCR analysis, the expression level of IFN-γ and iNOs was significantly increased (p < 0.001) in mice treated with 32.5, 75, 150 mg/kg/day for two weeks. CONCLUSION: The obtained findings of the current investigation exhibit the significant prophylactic effects of ZnNPs against chronic toxoplasmosis in mice; so that oral administration of ZnNPs the doses 32.5, 75, 150 mg/kg reduced the parasite load and even completely controlled the infection in mice. The results show that the ZnNPs had strengthened the innate immune system which could be the reason for its strong prophylactic effects. However, further in vivo and clinical investigations are required to confirm these results as well as other possible mechanisms that can trigger these pharmacological properties.
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INTRODUCTION: Many agents disrupt the cell cycle and its signaling circuits leading to cancer progress. Cancer therapy is performed by surgery, radiation, and chemical drugs remaining some side effects. OBJECTIVE: To evaluate the anticancer traits of herbal medicines. METHODS: We collected previously published data in searching engines (Web of Science, PubMed, Medline, and SCOPUS) by searching key words "herbal medicine," "anticancer effect," "compounds," and "fractions." RESULTS: Herbal medicines have unraveled anticancer effects mostly through cancer cells apoptosis via blocking NF-κB pathway by curcumin and terpenoides; CD95 signaling and enhancement of CD95L expression by resveratrol; and inhibiting tyrosine kinas, angiogenesis, and cell cycle arrest in G2/M phase by ß-lapachone-genistein and cytochrome-c release into the cytosol and caspase-9 activation by biocalein and quercetin. Additionally, impeding cell cycle in the G1 phase in ovarian cancer cells by 7-hydroxystaurosporine, immune cells enrichment (neutrophils and NK cells activation by Viscum album L., T cells and NK cells activation and cytokines such as tumor necrosis factor release by Ganoderma lucidum and microRNAs regulation (by Sinomeniumacutum, shikonin, Oleaeuropaea, curcumin and ginseng). These effects have implications for proper cancer cells elimination. It has been revealed that cytotoxic effects of herbal compounds (mostly those secondary metabolites) have exerted anticancer properties against several cancer cell lines. In addition, targeting microRNAs, nanoparticle-assisted herbal synergism, and novel drug delivery systems and combination chemotherapies have also emerged exerting higher efficacies for specific cell targeting as novel cancer therapy approaches. CONCLUSION: Considering side effects, toxicity, and higher costs of common cancer therapy approaches, application of novel herbal medicine-based therapies will confer promising insights for health outcomes.