STING pathway as a cancer immunotherapy: Progress and challenges in activating anti-tumor immunity.

The stimulator of the interferon genes (STING) signaling pathway plays a crucial role in innate immunity by detecting cytoplasmic DNA and initiating antiviral host defense mechanisms. The STING cascade is triggered when the enzyme cyclic GMP-AMP synthase (cGAS) binds cytosolic DNA and synthesizes the secondary messenger cGAMP. cGAMP activates the endoplasmic reticulum adaptor STING, leading to the activation of kinases TBK1 and IRF3 that induce interferon production. Secreted interferons establish an antiviral state in infected and adjacent cells. Beyond infections, aberrant DNA in cancer cells can also activate the STING pathway. Preclinical studies have shown that pharmacological STING agonists like cyclic dinucleotides elicit antitumor immunity when administered intratumorally by provoking innate and adaptive immunity. Combining STING agonists with immune checkpoint inhibitors may improve outcomes by overcoming tumor immunosuppression. First-generation STING agonists encountered challenges like poor pharmacokinetics, limited tumor specificity, and systemic toxicity. The development of the next-generation STING-targeted drugs to realize the full potential of engaging this pathway for cancer treatment can be a solution to overcome the current challenges, but further studies are required to determine optimal applications and combination regimens for the clinic. Notably, the controlled activation of STING is needed to preclude adverse effects. This review explores the mechanisms and effects of STING activation, its role in cancer immunotherapy, and current challenges.

Long non-coding RNAs and JAK/STAT signaling pathway regulation in colorectal cancer development.

Colorectal cancer (CRC) is one of the main fatal cancers. Cell signaling such as Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling substantially influences the process of gene expression and cell growth. Long non-coding RNAs (lncRNAs) play regulatory roles in cell signaling, cell proliferation, and cancer fate. Hence, lncRNAs can be considered biomarkers in cancers. The inhibitory or activating effects of different lncRNAs on the JAK/STAT pathway regulate cancer cell proliferation or tumor suppression. Additionally, lncRNAs regulate immune responses which play a role in immunotherapy. Mechanisms of lncRNAs in CRC via JAK/STAT regulation mainly include cell proliferation, invasion, metastasis, apoptosis, adhesion, and control of inflammation. More profound findings are warranted to specifically target the lncRNAs in terms of activation or suppression in hindering CRC cell proliferation. Here, to understand the lncRNA cross-talk in CRC through the JAK/STAT signaling pathway, we collected the related in vitro and in vivo data. Future insights may pave the way for the development of novel diagnostic tools, therapeutic interventions, and personalized treatment strategies for CRC patients.

Metallic Nanoparticles: Their Potential Role in Breast Cancer Immunotherapy via Trained Immunity Provocation.

Owing to drawbacks in the current common cancer therapies including surgery, chemotherapy and radiotherapy, the development of more reliable, low toxic, cost-effective and specific approaches such as immunotherapy is crucial. Breast cancer is among the leading causes of morbidity and mortality with a developed anticancer resistance. Accordingly, we attempted to uncover the efficacy of metallic nanoparticles (MNPs)-based breast cancer immunotherapy emphasizing trained immunity provocation or innate immunity adaptation. Due to the immunosuppressive nature of the tumor microenvironment (TME) and the poor infiltration of immune cells, the potentiation of an immune response or direct combat is a goal employing NPs as a burgeoning field. During the recent decades, the adaptation of the innate immunity responses against infectious diseases and cancer has been recognized. Although the data is in a scarcity with regard to a trained immunity function in breast cancer cells' elimination, this study introduced the potential of this arm of immunity adaptation using MNPs.

Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

In silico design and validation of a novel multi-epitope vaccine candidate against structural proteins of Chikungunya virus using comprehensive immunoinformatics analyses.

Chikungunya virus (CHIKV) is an emerging viral infectious agent with the potential of causing pandemic. There is neither a protective vaccine nor an approved drug against the virus. The aim of this study was design of a novel multi-epitope vaccine (MEV) candidate against the CHIKV structural proteins using comprehensive immunoinformatics and immune simulation analyses. In this study, using comprehensive immunoinformatics approaches, we developed a novel MEV candidate using the CHIKV structural proteins (E1, E2, 6 K, and E3). The polyprotein sequence was obtained from the UniProt Knowledgebase and saved in FASTA format. The helper and cytotoxic T lymphocytes (HTLs and CTLs respectively) and B cell epitopes were predicted. The toll-like receptor 4 (TLR4) agonist RS09 and PADRE epitope were employed as promising immunostimulatory adjuvant proteins. All vaccine components were fused using proper linkers. The MEV construct was checked in terms of antigenicity, allergenicity, immunogenicity, and physicochemical features. The docking of the MEV construct and the TLR4 and molecular dynamics (MD) simulation were also performed to assess the binding stability. The designed construct was non-allergen and was immunogen which efficiently stimulated immune responses using the proper synthetic adjuvant. The MEV candidate exhibited acceptable physicochemical features. Immune provocation included prediction of HTL, B cell, and CTL epitopes. The docking and MD simulation confirmed the stability of the docked TLR4-MEV complex. The high-level protein expression in the Escherichia coli (E. coli) host was observed through in silico cloning. The in vitro, in vivo, and clinical trial investigations are required to verify the findings of the current study.

Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment.

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.

Applications of Metallic Nanoparticles in the Skin Cancer Treatment.

Skin cancer is one of leading cancers globally, divided into two major categories including melanoma and nonmelanoma. Skin cancer is a global concern with an increasing trend, hence novel therapies are essential. The local treatment strategies play a key role in skin cancer therapy. Nanoparticles (NPs) exert potential applications in medicine with huge advantages and have the ability to overcome common chemotherapy problems. Recently, NPs have been used in nanomedicine as promising drug delivery systems. They can enhance the solubility of poorly water-soluble drugs, improve pharmacokinetic properties, modify bioavailability, and reduce drug metabolism. The high-efficient, nontoxic, low-cost, and specific cancer therapy is a promising goal, which can be achieved by the development of nanotechnology. Metallic NPs (MNPs) can act as important platforms. MNPs development seeks to enhance the therapeutic efficiency of medicines through site specificity, prevention of multidrug resistance, and effective delivery of therapeutic factors. MNPs are used as potential arms in the case of cancer recognition, such as Magnetic Resonance Imaging (MRI) and colloidal mediators for magnetic hyperthermia of cancer. The applications of MNPs in the cancer treatment studies are mostly due to their potential to carry a large dose of drug, resulting in a high concentration of anticancer drugs at the target site. Therefore, off-target toxicity and suffering side effects caused by high concentration of the drug in other parts of the body are avoided. MNPs have been applied as drug carriers for the of improvement of skin cancer treatment and drug delivery. The development of MNPs improves the results of many cancer treatments. Different types of NPs, such as inorganic and organic NPs have been investigated in vitro and in vivo for the skin cancer therapy. MNPs advantages mostly include biodegradability, electrostatic charge, good biocompatibility, high drug payload, and low toxicity. However, the use of controlled-release systems stimulated by electromagnetic waves, temperature, pH, and light improves the accumulation in tumor tissues and improves therapeutic outcomes. This study (2019-2022) is aimed at reviewing applications of MNPs in the skin cancer therapy.

The Antibacterial and Anti-biofilm Traits of the Novel BMAP-27-Melittin Conjugated Peptide Nanoparticle Against Streptococcus mutans: Clinical Isolates from Oral Cavity.

Background & Objective: The spread and development of drug-resistant bacterial strains has prompted the hunt for novel antibacterial polypeptides undergoing conformational changes to confer rapid bactericidal effects. The aim of this study was to evaluate the effect of novel BMAP27-Melittin conjugated peptide- nanoparticle (NP) against Streptococcus mutans as the primary pathogen from subgingival plaques. Methods: Sixty subgingival plaque samples were collected, and 39 S. mutans isolates were identified. The BMAP27-Melittin conjugated peptide was purchased from GenScript Company, USA. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Biofilm Inhibitory Concentration (BIC), and Biofilm Eradication Concentration (BEC) of BMAP27-Melittin-NP were calculated using the microtiter method. Results: Thirty-nine infected subjects were reported, including 24 males and 15 females (P=0.299). MIC, MBC, BIC, and BEC of BMAP27-Melittin-NP against S. mutans were 1.8, 2.9, 2.1, and 3.8µg/mL, respectively. The mean MBC, BEC, and BIC values were significantly lower among clinical isolates than S. mutans ATCC 35688 standard strain (P=0.032, 0.001, and 0.001, respectively). Conclusion: BMAP27-Melittin-NP demonstrated significant antibacterial and anti-biofilm effects against clinical isolates of S. mutans which can be considered a promising compound to prevent or treat dental caries and eradicate the oral infections.

The Effect of LL37 Antimicrobial Peptide on FOXE1 and lncRNA PTCSC 2 Genes Expression in Colorectal Cancer (CRC) and Normal Cells.

OBJECTIVE: As an innate immune system component, antimicrobial peptides (AMPs) exert various effects, such as anticancer properties. This study aimed to evaluate the LL37 AMP anticancer effect against colorectal cancer (CRC) cells and the expression of FOXE1 and lncRNA PTCSC2 genes. METHODS: The LL37 AMP was purchased from GenScript USA, Inc. Various CRC cell lines (HCT-116, HT29, WiDr, and SW742) were cultured in the DMEM medium. Various concentrations ranging from (5-400) µg/mL of LL37 AMP were prepared, added to cell cultures, and incubated for (24 and 48) hours. A nontoxic level of 30 µg/mL of LL37 was investigated for FOXE1 and lncRNA PTCSC2 gene expression. RESULTS: At 24 hours, the (50 and 90) % lethal concentrations of LC50 and LC90, respectively, of LL37 against NCM460 normal cells were (640 and > 640) g/mL. Additionally, these values at 48 hours included (160 and > 640) µg/mL, respectively. After 24 hours of treatment, the LC50 and LC90 of LL37 AMP against CRC cell lines included (20 and 200) µg/mL. The LC50 and LC90 of the LL37 at 48 hours included (20 and 50) µg/mL and at 72 hours. they included (~10 and 40) µg/mL, respectively. FOXE1 but not the PTCSC 2 gene expression was significantly higher in CRC cells than normal cells (NCM460 and HaCaT). The LL37 AMP significantly decreased FOXE1 gene expression by 1.95-fold in CRC cells (p < 0.001). CONCLUSION: The FOXE1 gene can be considered a biomarker of CRC development. The expression of FOXE1 but not the PTCSC2 gene was significantly affected by the LL37 AMP. The effects of LL37 AMP against CRC cells were time and dose-dependent. Future studies are warranted to verify these effects.

Nickel Nanoparticles: Applications and Antimicrobial Role against Methicillin-Resistant Staphylococcus aureus Infections.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved vast antibiotic resistance. These strains contain numerous virulence factors facilitating the development of severe infections. Considering the costs, side effects, and time duration needed for the synthesis of novel drugs, seeking efficient alternative approaches for the eradication of drug-resistant bacterial agents seems to be an unmet requirement. Nickel nanoparticles (NiNPs) have been applied as prognostic and therapeutic cheap agents to various aspects of biomedical sciences. Their antibacterial effects are exerted via the disruption of the cell membrane, the deformation of proteins, and the inhibition of DNA replication. NiNPs proper traits include high-level chemical stability and binding affinity, ferromagnetic properties, ecofriendliness, and cost-effectiveness. They have outlined pleomorphic and cubic structures. The combined application of NiNPs with CuO, ZnO, and CdO has enhanced their anti-MRSA effects. The NiNPs at an approximate size of around 50 nm have exerted efficient anti-MRSA effects, particularly at higher concentrations. NiNPs have conferred higher antibacterial effects against MRSA than other nosocomial bacterial pathogens. The application of green synthesis and low-cost materials such as albumin and chitosan enhance the efficacy of NPs for therapeutic purposes.

Opportunities and obstacles for the melanoma immunotherapy using T cell and chimeric antigen receptor T (CAR-T) applications: a literature review.

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.

The Characters of Graphene Oxide Nanoparticles and Doxorubicin Against HCT-116 Colorectal Cancer Cells In Vitro.

PURPOSE: Colorectal cancer (CRC) is among the leading causes of cancer death worldwide. Graphene oxide (GO) plus doxorubicin (DOX) have low toxicity and facilitate drug carriage and provide enough surface. The GO-DOX anticancer effects against HCT-116 human CRC cells were compared with that of pure GO and DOX compounds. METHODS: Different concentrations of graphene oxide (GO), doxorubicin (DOX), and graphene oxide plus doxorubicin (GO-DOX) were prepared. The MTT test was conducted to determine the viability of cells and flow cytometry was performed following DOX, GO, and GO-DOX exposure. Expressions of caspase 3, Bax, and ATG5 autophagy-related genes were investigated using RT-qPCR technique. RESULTS: In the MTT test, DOX and GO at 100 µg/mL and 40 µg/mL exerted 50% cell death (LC50) against the HCT-116 cells. We observed significant differences in GO-DOX LC50 at concentrations of 1 (p = 0.003), 2.5 (p = 0.003), 5 (p = 0.00009), and 10 µg/mL (p = 0.0001). The rate of apoptosis following GO, DOX, and GO-DOX included 24%, 31%, and 56%, respectively. The GO-DOX significantly increased the ATG5 (3.1-fold, p < 0.0001), caspase 3 (4.7-fold, p < 0.0001), and Bax (4.3-fold, p < 0.0001) gene expression. CONCLUSION: The GO-DOX exerted anticancer effects against the HCT-116 cells via inducing the apoptosis and autophagy.

Assessment of oncogenic role of intestinal microbiota in colorectal cancer patients.

INTRODUCTION: The direct association between some microbial species and cancers, such as in colorectal cancer (CRC), has been disclosed. OBJECTIVE: The aim of this study was to evaluate the changes in intestinal microbiota in subjects with CRC compared with healthy group. METHODS: Three-hundred fecal specimens were gathered from patients with CRC and 300 from healthy individuals during March 2014 to October 2019 from two hospitals in Tehran. The informed consent form and the questionnaire were completed by the patients. Following the identification of Lactobaccilus acidophilus (L. acidophilus), Lactobacillus palntarom (L. palntarom), and Enterococcus faecalis (E. faecalis), the number of bacteria was determined using quantitative real-time PCR (qPCR). RESULTS: The patients' age range was 20-76 years (mean: 55.34 ± 3.66). The qPCR clarified that number of E. faecalis was 2.2-fold higher in patients with CRC compared to healthy population (p = 0.0013). Additionally, the number of L. acidophilus and L. plantarom was 3.4-fold (p < 0.0001) and 4.8-fold (p < 0.0001) higher in healthy population. CONCLUSION: The inhibitory effect of intestinal microflora against the CRC development was proposed by observation of the changes in intestinal microbiota and determining their composition in subjects with CRC compared with that of healthy individuals. Microbiota was considered as a goal for the prevention and treatment of CRC. The relationship between microbiota and human health would be known deeper; this knowledge provides insights into the management of intestinal microbiota and therapeutics.

Anticancer Effects of Herbal Medicine Compounds and Novel Formulations: a Literature Review.

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.

Inhibitory Traits of Dendrosome Curcumin (DNC) on Breast Cancer Compared to Curcumin Single Compound.

PURPOSE: Vast therapeutic traits and very low toxicity of curcumin compound have made it and related formulations promising for treatment purposes. The aim of this study was the assessment of dendrosome curcumin (DNC) inhibitory effects on breast cancer therapy compared to single curcumin compound. METHODS: DNC was synthesized and MCF-7 cells were prepared. The cultured cells were treated with 20 µg/ml and 25 µg/ml of DNC. Real-time quantitative PCR (RT-qPCR) was performed to measure the expression of FOXCUT and MEG3 genes. Additionally, flow cytometry was applied to measure cell death rate and apoptosis. RESULTS: The results outlined that DNC enhanced the MEG3 gene expression significantly higher than the control. Furthermore, DNC was associated with a significant decrease in the expression of FOXCUT gene as compared to the control. The application of DNC in the MCF7 cell line enhanced cell death and reduced necrosis. CONCLUSIONS: The rate of apoptosis (programmed cell death) was enhanced, but necrosis was decreased in treated cancer cells compared to those treated with single curcumin. Accordingly, the DNC can be applied to hinder the growth and dissemination of cancer cells as a preferred approach to reduce the complications of other strategies such as chemotherapy and radiation therapy. Indeed, we concluded that DNC enhanced the expression of MEG3, a tumor suppressor, at 25 µm dose, but reduced the expression of the FOXCUT gene, possibly via the methylation of the gene. Thereby, DNC exerted a promising tumor inhibitory growth potential for the eradication of cancer cells.

Chemical Composition and Antimicrobial and Cytotoxic Activities of Foeniculum vulgare Mill Essential Oils.

BACKGROUND AND AIM: Foeniculum vulgare (F. vulgare) Mill, commonly known as fennel, belongs to the Umbelliferae (Apiaceae) family, biennial or perennial herbs disseminated in Mediterranean region and central Europe. This herbal medicine (HM) is considered as a traditional HM, and its parts have been studied. METHODS: In this survey, essential oils from seeds collected from three various regions (Kerman, Golestan, and East Azerbaijan Provinces) of Iran were prepared with hydro-distillation and their components were analyzed with gas chromatography (GC) and chromatography time-of-flight mass spectrometry (GC/MS). Antimicrobial and cytotoxic activities of the essential oils were examined with disk-diffusion method on Muller-Hinton agar and Subaru-dextrose Agar, respectively. Additionally, the MTT assay was assessed on breast cancer cell line (MCF-7). The expression of apoptosis-related genes, Bax and Bcl2, was determined using quantitative real-time PCR (RT-qPCR). RESULTS: The major fractions of essential oils identified by GC and GC/MS included trans-anethole (78.47%, 49.64%, 78.68%), fenchone (10.5%, 8.4%, and 10.2%), and limonene (5.9%, 6.70%, and 5.6%), respectively. Fennel oil collected from three various places exerted inhibitory effects on the bacterial growth and higher cytotoxic effects on MCF-7 cancer cell line. In addition, the essential oil increased the expression of Bax, but decreased Bcl2 gene expression significantly (P < 0.001). CONCLUSION: According to our findings, F. vulgare essential oil can be considered as a promising agent opening venues for novel antimicrobial and anticancer therapies. Owing to side effects and expensiveness of chemotherapy approaches, HM is a new remarkable insight for future therapies.

The Anticancer Efficiency of Citrullus colocynthis Toward the Colorectal Cancer Therapy.

BACKGROUND: Colorectal cancer (CRC) remains a major cause of death worldwide. Chemotherapy is associated with some side effects during CRC treatment. Hence, proper employment of lower toxic and approaches exerting lowest side effects are essential. The Citrullus colocynthis (C. colocynthis) seems a potential anticancerous herbal medicine (HM) against CRC mostly via various efficient compounds. METHODS: We performed a literature review regarding the anticancer traits of C. colocynthis against CRC. The possible active compounds, mechanisms, and combination therapies in vitro and in vivo or clinical trials have been also stated where found. RESULTS AND CONCLUSION: The anticancerous effects of C. colocynthis has been via a variety of pathways including apoptotic pathways (increase in caspase-3 and inhibiting STAT3 function), antioxidant and anti-inflammatory (TNF-α, nitric oxide, and pro-inflammatory cytokines such as IL-6, IL-8, and IL-1α) traits, inhibition of Wnt/ß-catenin signaling pathway, and antiangiogenesis and antimetastatic effects. Future studies will be promising regarding proper application of C. colocynthis compounds following their extraction.

Assessment of MMP29 Gene Expression and Silver Nanoparticles Effects on Colon Cancer Cell Line (HT29).

BACKGROUND: Colon cancer is a major cause of death around the world. The evaluation of novel approaches on corresponding genes would be a vital strategy toward eradication of cancer cells. In this study, the toxicity of silver nanoparticle on the colon cancer cell line (HT29) and expression of matrix metalloproteinase (MMP29) gene was investigated. MATERIALS AND METHODS: The silver nanoparticle (AgNPs) was synthesized and assessed by transmission electron microscopy (TEM). The cytotoxicity of synthesized AgNP on the HT29 cell line was evaluated using the MTT assay. Furthermore, the expression of MMP29 gene was investigated by the quantitative real-time PCR (RT-qPCR). RESULTS: The TEM results revealed that the fabricated AgNPs were mostly spherical in shape and had an average diameter of 22 nm. The results outlined that AgNPs significantly decreased the viability of cells in a dose- and time-dependent manner (p < 0.001). Additionally, we observed a significant difference among various concentrations. CONCLUSION: The findings indicated that the green fabricated AgNPs have the potential as a promising approach toward the colon cancer therapy. Furthered studies are essential to evaluate against other cancer cell lines and genes participating in the cancer progress.

Microbiome Dysbiosis and Predominant Bacterial Species as Human Cancer Biomarkers.

PURPOSE: To evaluate bacterial agents as cancer biomarkers. METHODS AND RESULTS: Various bacterial species have been demonstrated to involve in human cancers. However, the data is not enough for better understanding of predominant specific species. Application of a rapid and early-diagnostic, cost-effective, non-invasive, and inclusive method is a crucial approach for obtaining valid results. The role of Helicobacter pylori (H. pylori) in gastric and duodenal cancer has been confirmed. From investigation among previous publications, we attempted to make it clear which bacterial species significantly and specifically increase in various cancer types. It was unraveled that there is significant change in Granulicatella adiacens (G. adiacens) in lung cancer (LC), Fusobacterium nucleatum (F. nucleatum) in colorectal cancer (CRC), H. pylori and Porphyromonas gingivalis (P. gingivalis) in pancreatic cancer, and Streptococcus spp. in oral cancer. CONCLUSION: Alteration in the cell cycle by means of different mechanisms such as inflammation, alteration in cell signaling, invasion and immune evasion, specific niche colonization, induction of DNA damage and mutation, expression of some microRNAs, and enhancing epigenetic effects are the most common mechanisms employed by bacterial species.

Zataria Multiflora bois as an auspicious therapeutic approach against Echinococcus granulosus: Current status and future perspectives.

Hydatidosis caused by Echinococcus granulosus is a major zoonotic diseases. In addition to imposing heavy economic losses, the disease is a public health problem worldwide. The larval stage of the parasite (hydatid cyst) is formed in a wide range of domestic, wild and human beings as intermediate hosts. On the other, its recurrence has been reported anywhere as a reemerging disease. Although the cysts have some evading mechanisms, both human TH1 and TH2 cells subsets are stimulated. Because of increasing resistance and adverse effects of medications such as abnormalities of liver and other organs functions and abdominal pain, seeking alternative therapeutic approaches to be inexpensive, easy available, with low side effects and toxicity seems essential. However, the lack of information on the social and economic welfares of herbal medicines for the industrial scale application is a limitation. Zataria Multiflora bois (ZMB) has exhibited huge advantages and tremendous protoscolicidal effects as demonstrated by numerous studies and its combination therapies with anti-parasitic drugs have exerted desirable outcomes in vitro and in vivo. Noticeably, the compound confers negligible side effects or toxicity even at high concentrations. ZMB has exhibited promising inhibitory effects against hydatid cyst, particularly when combined with chemical drugs and in formulations of nanoemulsions. Its immunomodulatory effects include increase of nitric oxide production (NO) and protection of hepatic cells (Kupffer cells, fat-storing cells, and endothelial cells), enhancement of macrophages and T cells and increase of cytokines production. This study aimed at assessment of ZMB traits for application against hydatid cyst protoscolices.