Integration of phytotherapy and chemotherapy: Recent advances in anticancer molecular pathways.

Cancer is a disease characterized by abnormal and uncontrolled growth of cells, leading to invasion and metastasis to other tissues. Chemotherapy drugs are some of the primary treatments for cancer, which could detrimentally affect the cancer cells by various molecular mechanisms like apoptosis and cell cycle arrest. These treatment lines have always aligned with side effects and drug resistance. Due to their anticancer effects, medicinal herbs and their active derivative compounds are being profoundly used as complementary treatments for cancer. Many studies have shown that herbal ingredients exert antitumor activities and immune-modulation effects and have fewer side effects. On the other hand, combining phytotherapy and chemotherapy, with their synergistic effects, has gained much attention across the medical community. This review article discussed the therapeutic effects of essential herbal active ingredients combined with chemotherapeutic drugs in cancer therapy. To write this article, PubMed and Scopus database were searched with the keywords "Cancer," "Combination," "Herbal," "Traditional," and "Natural." After applying inclusion/exclusion criteria, 110 articles were considered. The study shows the anticancer effects of the active herbal ingredients by inducing apoptosis and cell cycle arrest in cancer cells, especially with a chemotherapeutic agent. This study also indicates that herbal compounds can reduce side effects and dosage, potentiate anticancer responses, and sensitize cancer cells to chemotherapy drugs.

Expression and Alteration Value of Long Noncoding RNA AB073614 and FER1L4 in Patients with Acute Myeloid Leukemia (AML).

BACKGROUND: Numerous studies have probed the deregulation of the long noncoding RNA AB073614 and FER1L4, which have been discovered in a variety of cancers. However, the precise expression pattern of these lncRNAs and their clinical implications in acute myeloid leukemia (AML) remain elusive. Considering the involvement of the PI3K axis in AML pathogenesis, an investigation into the expression of AB073614 and FER1L4 targets of this pathway has been proposed, aiming to elucidate a potential mechanism underlying AML development. METHODS: The expression levels of lncRNA AB073614 and FER1L4 were assessed in 30 newly diagnosed AML patients and 12 healthy individuals using quantitative reverse transcription-polymerase chain reaction techniques. A statistical analysis was conducted to determine the association of AB073614 and FER1L4 expression levels with clinicopathological features. RESULTS: A significant upregulation of AB073614 was observed in AML patients compared to the control group (p < 0.05). Moreover, a notable increase in AB073614 expression levels coincided with a significant reduction in FER1L4 expression levels in AML samples (p < 0.05). The diagnostic value of these lncRNAs was validated using the receiver operating characteristic (ROC) curve and area under the curve (AUC) calculations. Sensitivity values of AB073614 and FER1L4 gene expression were 96.7% and 100%, respectively, using cut-off relative quantification of 1.045 and 0.770. Additionally, specificity values were observed to be 100%. CONCLUSIONS: The present study indicates that AB073614 and FER1L4 might serve as prognosis biomarkers in AML patients. However, further detailed examinations in this field are warranted. It is proposed that the likely mechanism of imbalanced PI3K and PTEN activity, triggered by the deregulation of AB073614 and FER1L4, may have a crucial role in AML pathogenesis. Any component of this pathway could potentially serve as a new target for more insightful treatment approaches.

The Anti-inflammatory Effect of Ginger Extract on the Animal Model of Multiple Sclerosis.

Background: Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes. Objective: To investigate ginger extract's effect on reducing inflammation and improving the symptoms in the EAE model. Methods: The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-ß), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation. Results: The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups. Conclusion: The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.

Chamomile and Urtica dioica extracts improve immunological and histological alterations associated with polycystic ovarian syndrome in DHEA -induced mice.

BACKGROUND: One of the novel mechanisms in the pathogenesis of Polycystic ovary syndrome (PCOS) is low-grade chronic inflammation. Chamomile (Matricaria recutita L.) and Nettle (Urtica dioica), with phytoestrogenic and antioxidant properties, are traditionally used to treat gynecological diseases. This study investigated the immune-modulating effects of these two plants. METHODS: Following the induction of PCOS by subcutaneous injection (SC) of Dehydroepiandrosterone (DHEA) in BALB / C mice. Mice were treated in five groups: Sham, PCOS, PCOS + Chamomile, PCOS + Nettle, and PCOS + Chamomile and Nettle for 21 days. Ovarian morphology, blood antioxidant capacity, the abundance of Treg cells, and expression of matrix metalloproteinase-9 (MMP-9), transforming growth factor-ß (TGF-ß), cyclooxygenase-2 genes (COX-2), and tumor necrosis factor-alpha (TNF-α) were measured. RESULTS: Folliculogenesis, Cystic follicles, and corpus luteum improved in the treatment groups (P < 0. 05). Treg cells in the DHEA group were significantly reduced compared to the Sham group (P < 0. 01). However, this decrease was not corrected in treatment groups (P > 0. 05). Total serum antioxidant capacity was significantly increased in the treatment group of Nettle and Chamomile + Nettle (P < 0. 05). The expression of MMP9 and TGFß genes in the PCOS group was significantly higher than the Sham group (P < 0. 05), which the expression of MMP9 was corrected by treatment with Chamomile + Nettle extract (P < 0. 05). CONCLUSION: Chamomile and Nettle extract may be an effective supplement in improving the histological and immunological changes of PCOS. However, more research is needed to confirm its effectiveness in humans.

Synergistic apoptotic effects of ethanolic extracts of ginger and Ganoderma lucidum in a colorectal cancer cell line.

Current conventional therapy for colorectal cancer includes surgery, radiation and chemotherapy, all of which produce side effects. Herbal medicine can control the side effects of conventional treatments. We investigated the synergistic effect of a mixture of Zingiber officinale Roscoe (Ginger) and Ganoderma lucidum extracts on colorectal cancer cell apoptosis in vitro. We prepared ethanolic extracts of ginger (GEE) and G. lucidum (GLEE). Cytotoxicity was evaluated using MTT assay and the half-maximal inhibitory concentration (IC50) of each extract was calculated. The effect of these extracts on apoptosis in cancer cells was assessed using flow cytometry; Bax, Bcl2 and caspase-3 gene expression was evaluated using real-time PCR. GEE and GLEE decreased CT-26 cell viability significantly in a dose-dependent manner; however, the combined application of GEE + GLEE was most effective. Bax:Bcl-2 gene expression ratio, caspase-3 gene expression and the number of apoptotic cells were increased significantly in CT-26 cells treated at the IC50 level of each compound, especially in the GEE + GLEE treatment group. Combined ginger and Ganoderma lucidum extracts exhibited synergistic antiproliferative and apoptotic effects on colorectal cancer cells.

Anti-tumor effects of PEGylated-nanoliposomes containing ginger extract in colorectal cancer-bearing mice.

Objectives: This study aimed to develop a nanoliposomal formulation containing ginger ethanolic extract with a higher therapeutic effect for cancer treatment. Materials and Methods: The present study aimed to prepare PEGylated nanoliposomal ginger through the thin film hydration method plus extrusion. Physicochemical characteristics were evaluated, and the toxicity of the prepared liposomes was assessed using the MTT assay. In addition, tumor size was monitored in colorectal cancer-bearing mice. Also, the anticancer effects of liposomal ginger were evaluated by gene expression assay of Bax and Bcl-2 and cytokines including TNF-α, TGF-ß, and IFN-γ by Real-time PCR. Also, cytotoxic T lymphocytes (CTLs) and regulatory T lymphocytes (Treg cells) were counted in spleen and tumor tissue by flow cytometry assay. Results: The nanoliposomes' particle size and polydispersity index (PDI) were 94.95 nm and 0.246 nm, respectively. High encapsulation capacity (80 %) confirmed the technique's efficiency, and the release rate of the extract was 85% at pH 6.5. In addition, this study showed that liposomal ginger at 100 mg/kg/day enhanced the expression of Bax (P<0.05) and IFN-γ (P<0.01) compared with ginger extract in the mouse model. Also, the number of tumor-infiltrating lymphocytes (TILs) and CTLs cell count in tumor tissue showed a significant increase in the LipGin group compared with the Gin group (P<0.05). Conclusion: Results indicated that the liposomal ginger enhanced the antitumor activity; therefore, the prepared liposomal ginger can be used in future clinical trials.

The immune system's role in PCOS.

Polycystic ovary syndrome (PCOS) is a common disorder of the endocrine system. Its main manifestations include oligo-ovulation, hyperandrogenism, and polycystic ovary morphology (PCOM), affecting women of childbearing age. Although the exact pathogenesis of this disease is still unknown, many factors, including genetic, endocrine, and metabolism disorders, play critical roles in its development. The immunopathogenesis of PCOS has not yet been studied in-depth, but it is hypothesized that immune system abnormalities may play a key role in it. Recent research has shown inflammation's effect on ovulation and ovarian follicular dynamics. Thus, it is suggested that there is a close association between PCOS and low-grade chronic systemic inflammation. As a result, chronic low-grade inflammation is identified as a significant factor in the pathogenesis and development of PCOS, which in turn leads to infertility. As a result, this article reviews PCOS immunopathology, evaluates long-standing hypotheses about the immune system's role in PCOS, and assesses the association between inflammatory factors and PCOS.

Biochanin-A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF-ß1 and PAR-2 genes expression in kidney tissues of STZ-induced diabetic rats.

One of the major complications of diabetes is diabetic nephropathy, and often many patients suffer from diabetic nephropathy. That is why it is important to find the mechanisms that cause nephropathy and its treatment. This study was designed to examine the antidiabetic effects of biochanin A (BCA) and evaluate its effects on oxidative stress markers and the expression of transforming growth factor-ß1 (TGF-ß1) and protease-activated receptors-2 (PAR-2) genes in the kidney of type 1 diabetic rats. After induction of diabetes using streptozotocin (STZ), 55 mg/kg bw dose, rats were randomly divided into four groups with six rats in each group as follows: normal group: normal control receiving normal saline and a single dose of citrate buffer daily; diabetic control group: diabetic control receiving 0.5% dimethyl sulfoxide daily; diabetic+BCA (10 mg/kg) group: diabetic rats receiving biochanin A at a dose of 10 mg/kg bw daily; diabetic+BCA (15 mg/kg) group: diabetic rats receiving biochanin A at a dose of 15 mg/kg bw daily. TGF-ß1 and PAR-2 gene expression was assessed by real-time. Spectrophotometric methods were used to measure biochemical factors: fast blood glucose (FBG), urea, creatinine, albumin, lipids profiles malondialdehyde (MDA), and superoxide dismutase (SOD). The course of treatment in this study was 42 days. The results showed that in the diabetic control group, FBG, serum urea, creatinine, expression of TGF-ß1 and PAR-2 genes, and the levels of MDA in kidney tissue significantly increased and SOD activity in kidney tissue and serum albumin significantly decreased compared to the normal group (p < 0.001). The results showed that administration of biochanin A (10 and 15 mg/kg) after 42 days significantly reduced the expression of TGF-ß1 and PAR-2 genes and FBG, urea, creatinine in serum compared to the diabetic control group (p < 0.001), also significantly increased serum albumin compared to the diabetic control group (p < 0.001). The level of MDA and SOD activity in the tissues of diabetic rats that used biochanin A (10 and 15 mg/kg) was significantly reduced and increased, respectively, compared to the diabetic control group (p < 0.001). Also, the result showed that in the diabetic control group lipids profiles significantly is disturbed compared to the normal group (p < 0.001), the results also showed that biochanin A (10 and 15 mg/kg) administration could significantly improved the lipids profile compared to the control diabetic group (p < 0.001). It is noteworthy that it was found that the beneficial effects of the biochanin A were dose dependent. In conclusion, administration of biochanin A for 42 days has beneficial effect and improves diabetes and nephropathy in diabetic rats. So probably biochanin A can be used as an adjunct therapy in the treatment of diabetes.

Anti-Inflammatory Activity of S. Marianum and N. Sativa Extracts on Macrophages.

BACKGROUND: Nigella sativa (N. sativa) and Silybum marianum (S. marianum) are used to regulate macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells and thioglycollate-elicited peritoneal inflammation. METHODS: Cytotoxicity assays and acute toxicity tests were performed to investigate the safe dose and toxicity of the prepared extracts. Also, nitric oxide production was determined by Griess assay on RAW264.7 and peritoneal macrophage supernatants. After RNA extraction from macrophages, real-time PCR was performed to measure the relative gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-ß, and IL-10. Finally, regulatory T cells (Treg cells) were counted by flow cytometry. RESULTS: S. marianum methanolic extract (SME), N. sativa ethanolic extract (NEE), and their mixture (SME+NEE) decreased NO levels significantly in RAW264.7 and peritoneal murine macrophages. N. sativa ethanolic extract significantly increased IL-10 gene expression and significantly decreased IL-6 and TNF-α expression in RAW264.7 cells. In mixture-treated peritoneal macrophages, IL-10 and TGF-ß expression were significantly increased, while IL-6 and TNF-α were significantly decreased. Also, the percentage of Treg cells was significantly greater in the mixture-treated cells than in controls. CONCLUSION: These results suggest that an SME and NEE mixture has anti-inflammatory and immunomodulatory activities and may be useful in the treatment of diseases of immunopathologic origin characterized by macrophage hyperactivation.

Reduced IL-37 gene expression and CD8 T lymphocytes in patients with metastatic breast cancer.

BACKGROUND: The exact immunopathological mechanisms in the progression of breast cancer are not clearly understood, but various factors including CD8 T lymphocytes have lethal properties on tumor cells. On the other hand, interleukin-37 (IL-37), as a new member of the IL-1 family, is an anti-inflammatory cytokine. The exact role of IL-37 in breast cancer has not yet been determined. OBJECTIVE: This study aimed to evaluate the CD8 T lymphocytes count and IL-37 gene expression in newly diagnosed breast cancer patients with and without metastasis. METHODS: In this study, blood samples from 36 metastatic and 36 non-metastatic breast cancer patients and 36 healthy individuals as control were collected. After RNA extraction and cDNA synthesis, the relative gene expression was performed using real-time PCR. Also, counting the CD8 T lymphocytes was done by flow cytometry technique. RESULTS: The results of this study showed that the gene expression of IL-37 in blood samples of metastatic and non-metastatic breast cancer patients was significantly lower than in healthy individuals (P < 0.05). The relative gene expression of the IL-37 in ER+/PR+/HER2+ patients with non-metastatic breast cancer had a significant increase compared to HER2+ patients (P < 0.05). Also, CD8 T lymphocytes count in the samples of patients including non-metastatic and metastatic breast cancer was significantly decreased compared to the healthy individuals (P < 0.05). CONCLUSIONS: Our findings provide evidence that IL-37 gene expression and CD8 T lymphocytes count, significantly decreased in non-metastatic and metastatic breast cancer. Considering the possible effects of IL-37 on TCD8 cells in tumor immune responses, more research will be done to benefit from the therapeutic effects of this cytokine in the future.

Protective Effects of Curcumin against Lipopolysaccharide-Induced Toxicity.

BACKGROUND: Lipopolysaccharide (LPS), a Gram-negative bacterial cell wall component, evokes intensive inflammatory responses in the human body. Naturally, inflammation is a part of the host immune response to an infection; nonetheless, an exaggerated response can lead to a series of pathophysiological consequences, collectively known as LPS toxicity or septic shock. OBJECTIVE: This review will explore the cellular and experimental investigations that mainly focus on Curcumin's therapeutic effects on the LPS-mediated inflammatory responses. METHOD: A literature review of all relevant studies was performed. CONCLUSION: Curcumin has been reported to exert anti-inflammatory properties by interfering with LPS-induced inflammatory pathways, including binding to cell surface receptors of LPS, NF-kB activation pathway, and inflammasome activation. Further clinical studies on the effect of Curcumin in reducing the pathophysiological consequences of LPS toxicity would substantiate the use of this molecule for future therapeutic approaches.

Macrophage polarization by phytotherapy in the tumor microenvironment.

Several signaling pathways were involved in M1 (classic) and M2 (alternative) macrophage polarization. Disruption of M2-related signaling pathways and improvement of M1-related signaling pathways can be identified as one of the cancer therapeutic approaches. Prevention of macrophage differentiation into M2 by different herbal agents with antitumor properties can be considered as a promising therapeutic target for cancer patients. In the present review study, we investigated the effect of herbal compounds on M1 and M2 related signaling pathways to reduce M2 and increase M1 macrophage polarization for the treatment of different types of cancer.

Synergistic Evaluation of Ginger and Licorice Extracts in a Mouse Model of Colorectal Cancer.

Herbal medicine can be used to overcome the side effects of conventional treatments. This study aimed to evaluate the anticancer activities of ginger and licorice extracts, as well as the synergistic effects of their combination. Ginger ethanolic extract (GEE) and licorice methanolic extract (LME) were isolated by a Soxhlet extractor. Next, the anti-proliferative activity of the extracts, apoptosis induction, tumor growth inhibition, and tumor-infiltrating T lymphocytes were investigated. The MTT (3-[4, 5-dimethylthiazol-2-yl]-2, five diphenyl tetrazolium bromide) assay showed that GEE and LME decreased the CT26 cell viability in a dose-dependent manner; however, the GEE + LME combination was more effective (P < 0.05). The CT26 cells treated with each extract showed a significant increase in Bax/Bcl-2 ratio and caspase-3 gene expression, especially in the GEE + LME group (P < 0.001). Tumor volume significantly reduced in the GEE + LME group, compared to the negative controls. Finally, mice treated with GEE + LME showed a significant increase in the CTL/Treg cell ratio (P < 0.001) and Bax/Bcl2 ratio (P < 0.05). The study results revealed that GEE + LME can suppress cancer cell growth, increase apoptosis, and improve CTL infiltrating to the tumor site in a synergetic manner in-vivo and in-vitro. Therefore, the prepared mixture can be used in future clinical trials.

Cytokine profile and disease severity in patients with COVID-19.

Cytokine dysregulation is the proposed mechanism for Coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the serum levels of interferon (IFN)-γ, interleukin (IL)-5, IL-8, Il-9, IL-17, TGF-ß and IFN-γ in patients infected with SARS-CoV-2. The study was conducted between 63 adult patients with COVID-19 and compared with 33 age and gender-matched healthy subjects as controls. The age range in both groups was 50-70 years. The patients were classified into mild group (33 patients) and severe group (30 patients). Serum samples were collected from all participants and tested for the cytokine levels by ELISA (enzyme-linked immunosorbent assay) method. Statistical analysis was performed using the one-way ANOVA. The mean serum levels of IFN-γ, TGF-ß, IL-17 and IL-8 in the COVID-19 patients were significantly higher than those observed in the control group. A comparison of between the mild and severe groups showed significant differences in TGF-ß levels. The mean concentration of serum IL-5 and IL-9 in patients with COVID-19 did not differ from those in the control group. Systemic IL-17 levels correlated positively and significantly with TGF-ß in patients with COVID-19. Th1 (IFN-γ), Treg (TGF-ß), and Th17 (IL-17) cytokines concentration were increased in COVID-19 patients. Interferon-γ and IL-17 are involved in inducing and mediating proinflammatory responses. Our data suggest that TGF-ß can be used as a predictive factor of disease severity in patients with COVID-19.

In vivo therapeutic effects of colorectal cancer cell-derived exosomes.

OBJECTIVES: Exosomes are nano-sized structures with lipid bilayer membranes that can be secreted by cancer cells. They play an important role in the biology of the tumor extracellular matrix. Exosomes may contain and transfer tumor antigens to dendritic cells to trigger T cell-mediated anti-tumor immune responses. MATERIALS AND METHODS: BALB/c mice bearing CT26 colorectal cancer were treated subcutaneously with purified exosomes from analogous tumor cells. The mice were analyzed with respect to tumor size, survival, and anti-tumor immunity responses, including gene expression of cytokines and flowcytometry analysis of T lymphocytes. RESULTS: The rate of tumor size growth in the exosome-treated group significantly decreased (P<0.05), and the flow cytometry results showed a significant reduction in the spleen regulatory T cells (Tregs) count of the exosome-treated group, compared with the untreated group (P=0.02). Although the increase in the serum level of interferon-γ (IFN-γ) and the number of cytotoxic CD8 T lymphocytes (CTLs) in the spleen tissue was not significant (P>0.05), the gene expression of IFN-γ increased significantly (P=0.006). CONCLUSION: The present results revealed that subcutaneous administration of tumor-derived exosomes could effectively lead to the inhibition of tumor progression by decreasing the number of Treg cells and up-regulation of the IFN-γ gene. Therefore, tumor-derived exosomes can be used as potential vaccines in cancer immunotherapy.

Gene expression of semaphorin-3A, semaphorin-7A, neuropilin-1, plexin-C1, and ß1 integrin in treated-multiple sclerosis patients.

OBJECTIVE: Recently, members of the semaphorin family have received major attention in various medical fields, especially autoimmunity. In this study, we selected semaphorin-3A (Sema3A), semaphorin-7A (Sema7A), and their receptors to determine the possible relationship between these molecules and multiple sclerosis (MS). METHOD: We measured the gene expression of Sema3A, Sema7A, neuropilin-1 (NP-1), plexin-C1, and ß1 integrin in the blood samples of relapsing-remitting multiple sclerosis (RRMS) patients, treated with high-dose interferon-ß1a (IFN-ß1a), low-dose IFN-ß1a, IFN-ß1b, and glatiramer acetate (GA) via quantitative real-time polymerase chain reaction (qRT-PCR) assay, and then, compared the results of treatment-naive patients with the healthy controls. RESULTS: The gene expression of Sema3A (P = 0.02), NP-1 (P < 0.001), and plexin-C1 (P < 0.01) significantly decreased in the treatment-naive group, compared to the healthy controls. Sema3A significantly increased in all treated patients, compared to the treatment-naive patients (P < 0.001). However, expression of NP-1 (P < 0.001), plexin-C1 (P < 0.001), and ß1 integrin (P < 0.05) only increased in patients receiving high-dose IFN-ß1a, IFN-ß1b, and GA. Expression of Sema7A increased in only two groups of patients treated with IFN-ß1b (P < 0.001) and GA (P = 0.018), without any significant decrease in the treatment-naive group, compared to the healthy controls (P > 0.05). CONCLUSION: Our findings confirm that the presence of Sema3A, Sema7A, and their receptors can play critical roles in the treatment of MS patients. Therefore, they can be potential target molecules for MS treatment in the future.

Increased expression of CD8 marker on T-cells in COVID-19 patients.

BACKGROUND: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. METHODS: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. RESULTS: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). CONCLUSION: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.

Effects of interferon and glatiramer acetate on cytokine patterns in multiple sclerosis patients.

Multiple sclerosis (MS) is an unpredictable autoimmune disease, which causes neurodegeneration in the central nervous system. Since the main cause of MS remains obscure, in this study, we aimed to evaluate the serum levels of some cytokines, including interleukin-5 (IL-5), IL-8, IL-9, IL-17A, transforming growth factor-beta (TGF-ß), and interferon-gamma (IFN-γ) in relapsing-remitting (RR)-MS patients, treated with IFN-ß and glatiramer acetate (GA). Serum samples of RR-MS patients, treated with high-dose IFN-ß1a, low-dose IFN-ß1a, IFN-ß1b, and GA, were assessed by ELISA assay and then compared with the results of treatment-naive patients and healthy controls. The findings showed that the serum levels of IL-8, IL-9, and IFN-γ in treatment-naive patients were significantly higher than the healthy controls, while there was no significant difference in terms of other cytokines between the groups. A significant reduction was observed in the levels of IL-9 and IFN-γ, while there was a significant increase in TGF-ß level among patients treated with GA. IFN-ß1b resulted in a significant decline in the levels of IL-9 and TGF-ß. In addition to these findings, some cytokines were positively correlated in different groups. Overall, the present results support the inflammatory and aggravating effects of IL-8, IL-9, and IFN-γ on MS. Furthermore, based on the results reported in the GA treatment group, we suggest GA as an effective treatment for RR-MS patients.

Assessment of CCL27 and IL-11 in Multiple Sclerosis Patients Treated with Interferon-ß and Glatiramer Acetate.

INTRODUCTION: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease which involves the central nervous -system. Although the primary cause of MS is obscure, effects of some cytokine and chemokine patterns in both innate and adaptive immune systems have been described. -Objectives: Since limited studies have examined the role of interleukin (IL)-11 and chemokine CCL27 in MS, we aimed to identify changes in IL-11 and CCL27 gene expression and serum levels in relapsing-remitting MS (RRMS) patients, treated with interferon (IFN)-ß and glatiramer acetate (GA). METHODS: The serum level and gene expression of IL-11 and CCL27 were measured and compared between treatment-naïve MS patients and RRMS patients who were treated with high-dose IFN-ß1a, low-dose IFN-ß1a, IFN-ß1b, and GA via enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction. RESULTS: A significant decrease was observed in the serum level of CCL27 in treatment-naïve patients and IFN-ß1b-treated patients compared to the healthy controls. On the other hand, a significant increase was found in the protein level of CCL27 in low-dose and high-dose IFN-ß1a groups compared to the treatment-naïve group. In addition, CCL27 gene expression was higher in patients treated with GA than in the treatment-naïve group. There were no significant changes in the gene expression or protein level of IL-11 in all experimental groups. Additionally, a positive correlation was found between IL-11 and CCL-27. CONCLUSION: Our results suggest the inflammatory role of CCL27 in MS patients, while IFN-ß1a seems to play a compensatory role for this chemokine.

Methadone therapy modulate the dendritic cells of heroin addicts.

Evidence from various studies suggests that narcotics abuse may exert adverse immunomodulatory effects on immune responses. The aim of this research was to understand the effects of detoxification with methadone on the percentage of dendritic cells (DCs) and expression of its markers in heroin addicts. In this study, myeloid DCs (CD11c+) and plasmacytoid DCs (CD123+) were examined in two groups. These groups comprised of 20 healthy volunteers and 20 chronic heroin addicts, before and after detoxification with methadone. The percentages of myeloid DCs and plasmacytoid DCs were lower in addict subjects than in the control. The HLA-DR expression on DCs was significantly lower in addict subjects than in the control, whereas CD11c and CD123 expression in DCs subsets were increased in them. Most of these changes were modified after the methadone therapy. Dendritic cells are essential to the initiation of primary immune responses, therefore the disruption of their function can be one of the reasons for the increased prevalence of infections in heroin addicts. The methadone therapy can improve the imposed changes by heroin.