The oncogenic roles of bacterial infections in development of cancer.

Initiation of cancer is interconnected with different factors like infections. It has been estimated that infections, particularly viruses, participate in about 20% of all cancers. Bacteria as the most common infectious agents are also reported to be emerging players in the establishment of malignant cells. Microbial infections are able to modulate host cell transformation for promoting malignant features through the production of carcinogenic metabolites participating in inflammation responses, disruption of cell metabolism, and integrity and also genomic or epigenetic manipulations. It seems that the best example of the role of bacteria in cancer promotion is Helicobacter pylori infection, which is related to gastric cancer. World Health Organization (WHO) describes bacterium as class I carcinogens. Several bacterial infections have been reported in association with prevalent cancers. In this review, we will summarize the role of known bacterial infections in the initiation of the main common cancers, which show high mortality in the world. Examining the microbiomes in cancer patients is important and necessary to better understand the pathogenesis of this disease and also to plan therapeutic interventions.

Synthesis and application of magnetic@layered double hydroxide as an anti-inflammatory drugs nanocarrier.

BACKGROUND: Magnetic nanocomposites with a core-shell nanostructure have huge applications in different sciences especially in the release of the drugs, because of their exclusive physical and chemical properties. In this research, magnetic@layered double hydroxide multicore@shell nanostructure was synthesized by the facile experiment and is used as novel drug nanocarrier. METHODS: Magnetic nanospheres were synthesized by a facile one-step solvothermal route, and then, layered double hydroxide nanoflakes were prepared on the magnetic nanospheres by coprecipitation experiment. The synthesized nanostructures were characterized by FTIR, XRD, SEM, VSM, and TEM, respectively. After intercalation with Ibuprofen and Diclofenac as anti-inflammatory drugs and using exchange anion experiment, the basal spacing of synthesized layered double hydroxides was compared with brucite nanosheets from 0.48 nm to 2.62 nm and 2.22 nm, respectively. RESULTS: The results indicated that Ibuprofen and Diclofenac were successfully intercalated into the interlay space of LDHs via bridging bidentate interaction. In addition, in-vitro drug release experiments in pH 7.4, phosphate-buffered saline (PBS) showed constant release profiles with Ibuprofen and Diclofenac as model drugs with different lipophilicity, water solubility, size, and steric effect. CONCLUSION: The Fe3O4@LDH-ibuprofen and Fe3O4@LDH-diclofenac had the advantage of the strong interaction between the carboxyl groups with higher trivalent cations by bridging bidentate, clarity, and high thermal stability. It is confirmed that Fe3O4@LDH multicore-shell nanostructure may have potential application for constant drug delivery.

In Silico Study and Optimization of Bacillus megaterium alpha-Amylases Production Obtained from Honey Sources.

This study aimed to screen alpha-amylase producing microorganisms from honey as a low water activity medium, a suitable source for selecting stable and cost-beneficial bacterial enzyme production systems. Plackett-Burman method was used to select twelve effective factors including pH, inoculum size, temperature, time, corn starch, KH2PO4, peptone, MgSO4, CaCl2, NaCl, glycerin, and yeast extract concentrations on bacterial alpha-amylases production yield. The Box-Behnken method was utilized to optimize the level of selected significant factors. The stability of bacterial alpha-amylases was also determined in low pH and high-temperature conditions. In addition, in silico study was used to create the alpha-amylase structure and study the stability in high-temperature and low water available condition. Among all isolated and characterized microorganisms, Bacillus megaterium produced the highest amount of alpha-amylases. The in silico data showed the enzyme 3D structure similarity to alpha-amylase from Halothermothrix orenii and highly negative charge amino acids on its surface caused the enzyme activity and stability in low water conditions. Based on Box-Behnken results, the temperature 35 °C, pH 6 and starch 40 g/l were determined as the optimum level of significant factors to achieve the highest alpha-amylases unit (101.44 U/ml). This bacterial alpha-amylases enzyme showed stability at pH 5 and a range of temperatures from 40 to 60 °C that indicates this enzyme may possess the potential for using in industrial processes.

Synthesis of Zeolitic imidazolate frameworks-8@ layered double hydroxide polyhedral nanocomposite with designed porous voids as an effective carrier for anti-cancer drug-controlled delivery.

In nanotechnology, compounds containing metal materials are used in pharmaceutical sciences. The main purpose of this research was to introduce a novel method to control the amount of zeolite imidazolate framework (ZIF) in water by forming a protective layer such as layered double hydroxide (LDH). Firstly, ZIF was synthesised as the nucleus of the nanocomposite, and then LDH was formed by in situ synthesis as a protective layer. Scanning electron microscope, Fourier-transform infrared spectroscopy, X-Ray Diffraction, and Brunauer, Emmett and Teller techniques were used to determine (ZIF-8@LDH chemical structure and morphology. Our findings revealed that the ZIF-8@LDH-MTX complex could interact with carboxyl groups and trivalent cations by creating a bifurcation bridge, clarity, and high thermal stability. The antibacterial test indicated that ZIF-8@LDH was able to inhibit pathogenic growth. 2,5-Diphenyl-2H-Tetrazolium Bromide assay results showed that ZIF-8@LDH alone had no notable cytotoxic effect on Michigan Cancer Foundation-7 (MCF-7) cancer cells. However, the cytotoxicity rate was significantly increased in treated MCF-7 cells with ZIF-8@LDH-MTX compared to that of treated cells with methotrexate alone, which can be reasoned by the protection of drug structure and increasing its permeability. The drug release profile was constant at pH = 7.4. All findings indicated that the ZIF-8@LDH complex could be considered a newly proposed solution for effective anti-cancer drug delivery.

Therapeutic Potential of Clostridium novyi-NT in Cancer: Current Knowledge and Future Perspectives.

Resistance to conventional antitumour therapies and Hypoxia in patients with advanced solid tumours are two major reasons for the failure of conventional anti-tumour therapies. Therefore, it is important to find a new therapeutic method that can overcome these problems. An attenuated anaerobic bacterium, Clostridium novyi-NT, could target Hypoxic and Necrotic areas of tumours causing tumour lysis and stimulating a host anti-tumour immune response. To the best of our knowledge, the combination of bacterial anti-tumour therapy, chemotherapy, radiotherapy and immunotherapy may promote tumour regression, inhibit metastasis and develop a new strategy for the treatment of solid tumours. However, the possible molecular mechanisms of the combined therapies are still the biggest challenge. This review provides an overview of the history of bacterial cancer therapy and the development of a non-lethal strain of Clostridium novyi. Below is a precise definition of Hypoxic conditions in solid tumour tissue. To understand the anticancer effect of Clostridium novyi-NT spores, possible cell death mechanisms were summarised by the enzyme phospholipase C (nt01cx0979), which is secreted by Clostridium novyi-NT spores after germination in tumour tissue. The function of Clostridium novyi-NT spores in stimulating the host immune system to elicit anti-tumour responses was reviewed. Then, the results of anti-tumour combination therapies based on Clostridium novyi-NT spores were compiled. Identifying the molecular mechanisms of Clostridium novyi-NT in treating tumours and inducing cell death in invasive cancer cells, ultimately leading to tumour regression, may develop promising clinical strategies in the combined treatment of solid tumours.

Anti-tumor Effects of Cisplatin Synergist in Combined Treatment with Clostridium novyi-NT Spores Against Hypoxic Microenvironments in a Mouse Model of Cervical Cancer Caused by TC-1 Cell Line.

Purpose: Despite the development of anti-human papillomavirus (HPV) vaccines, cervical cancer is still a common disease in women, especially in developing countries. The presence of a hypoxic microenvironment causes traditional treatments to fail. In this study, we presented a combined treatment method based on the chemotherapeutic agent cisplatin and Clostridium novyi-NT spores to treat normoxic and hypoxic areas of the tumor. Methods: TC-1 Cell line capable of expressing HPV-16 E6/7 oncoproteins was subcutaneously transplanted into female 6-8 week old C57/BL6 mice. The tumor-bearing mice were randomly divided into four groups and treated with different methods after selecting a control group. Group 1: Control without treatment (0.1 mL sterile PBS intratumorally), Group: C. novyi-NT (107 C. novyi-NT). Group 3: Receives cisplatin intraperitoneally (10 mg/kg). Fourth group: Intratumoral administration of C. novyi-NT spores + intraperitoneal cisplatin. Western blot analysis was used to examine the effects of anti-hypoxia treatment and expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins. Results: The results clearly showed that combined treatment based on C. novyi-NT and cisplatin significantly reduced the expression of HIF-1 alpha and VEGF proteins compared to cisplatin alone. At the same time, the amount of necrosis of tumor cells in the combined treatment increased significantly compared to the single treatment and the control. At the same time, the mitotic count decreased significantly. Conclusion: Our research showed that developing a combined treatment method based on C. novyi-NT and cisplatin against HPV-positive cervical cancer could overcome the treatment limitations caused by the existence of hypoxic areas of the tumor.

Modified gelatin/iron- based metal-organic framework nanocomposite hydrogel as wound dressing: Synthesis, antibacterial activity, and Camellia sinensis release.

A new kind of Camellia sinensis-loaded nanocomposite hydrogel based on modified gelatin/iron-metal-organic framework was developed as an antibacterial wound dressing. Gelatin as a biocompatible natural polymer was modified with methacrylate anhydride to produce gelatin methacrylate. Thereafter, acrylic acid and acrylamide were grafted on gelatin methacrylate during an aqueous polymerization process. To enhance the porosity, mechanical strength, and drug loading capability of the hydrogel and reduce its toxicity, iron- based metal-organic framework was incorporated within the hydrogel. To add more functionality to the final wound dressing, Camellia sinensis, an antibacterial herbal drug was loaded on the hydrogel. The structural and chemical properties of prepared nanocomposite hydrogel were investigated by FTIR, XRD, SEM, and TGA techniques. The incorporation of iron-based metal-organic framework within the hydrogel matrix led to an increase in its water absorption value from 400.10 to 547.96 (g/g). The release study of Camellia sinensis (CS) extract from the prepared nanocomposite hydrogel exhibited a sustained release manner. The antibacterial test revealed the nanocomposite hydrogel contain extract has an effective antibacterial function against "Bacillus serous", "Staphylococcus aureus", "Streptococcus mutans"," Escherichia coli", "Klebsiella pneumoniae", and "Pseudomonas aeruginosa" bacteria. Therefore, the synthesized nanocomposite is a good candidate as an antibacterial hydrogel wound dressing. .

Role of Fungal Infections in Carcinogenesis and Cancer Development: A Literature Review.

Cancer is a serious debilitating disease and one of the most common causes of death. In recent decades the high risk of various cancers enforced scientists to discover novel prevention and treatment methods to diminish the mortality of this terrifying disease. Accordingly, its prevention can be possible in near future. Based on epidemiological evidence, there is a clear link between pathogenic fungal infections and cancer development. This association is often seen in people with weakened immune systems such as the elderly and people with acquired immunodeficiency (AIDS). Carcinoma in these people is first seen chronically and then acutely. Although the different genetic and environmental risk factors are involved in carcinogenesis, one of the most important risk factors is fungal species and infections associating with cancers etiology. Now it is known that microbial infection is responsible for initiating 2.2 million new cancer cases. In this way, many recent studies have focused on investigating the role and mechanism of fungal infections in diverse cancers occurrence. This review provides a comprehensive framework of the latest clinical findings and the association of fungal infections with versatile cancers including esophageal, gastric, colorectal, lung, cervical, skin, and ovarian cancer.

Antimicrobial activity of Bacillus sp. isolated strains of wild honey.

BACKGROUND: Multi-drug resistant bacteria hazards to the health of humans could be an agent in the destruction of human generation. Natural products of Bacillus species are the main source to access progressive antibiotics that can be a good candidate for the discovery of novel antibiotics. Wild honey as a valuable food has been used in medicine with antimicrobial effects. OBJECTIVE: Bacillus strains isolated from wild honey were evaluated for the potential antimicrobial activity against human and plant bacterial and fungal pathogens. METHODS: Three bacterial isolates were identified as strain Khuz-1 (98.27% similarity with Bacillus safensis subsp. Safensis strain FO-36bT), strain Khuz-2 (99.18% similarity with Bacillus rugosus strain SPB7T), and strain Khuz-3 (99.78% similarity with Bacillus velezensis strain CR-502 T) by 16S rRNA gene sequences. The strains were characterized by their ability to inhibit the growth of human and phytopathogenic fungi. RESULTS: The results indicated that B. rugosus strain Khuz-2 inhibited the growth of phytopathogenic and human fungal more effective than other ones. It seems that the strain Khuz-2 has a suitable antimicrobial and antifungal potential as a good candidate for further pharmaceutical research. CONCLUSION: Based on the results of GC-MS, Pyrrolo [1,2-a] pyrazine-1,4-dion, hexahydro-3-(2-methylpropyle) (PPDHM) was the major compound for all strains which have a various pharmacological effect. Isolation and identification of beneficial bacteria from natural sources can play an important role in future pharmaceutical and industrial applications.

A novel method for the development of plasmid DNA-loaded nanoliposomes for cancer gene therapy.

We aimed to develop a simple yet novel method to prepare plasmid DNA-loaded nanoliposomes for cancer gene therapy. Murine interleukin-12 (mIL-12) pDNA-loaded nanoliposomes were prepared via novel freeze-drying of a monophase solution method. The physicochemical characteristics, cytotoxicity, and transfection efficiency of the prepared nanoliposomes in murine CT-26 colon carcinoma cells were evaluated. Furthermore, tumor progression and survival rate in CT-26 colon carcinoma-bearing BALB/c mice subsequent to direct intratumoral injections were investigated over a period of 40 days. Using this preparation method, nanoliposomes with particle size of around 300 nm and zeta potential of 96.5 mV were obtained. The transmission electron microscope results showed that the liposomes were nano-sized and almost spherical. The agarose gel retardation assay revealed the pDNA encapsulation in the nanoliposomes. The nanoliposomes with 72.4% encapsulation efficiency and low cell toxicity could significantly improve mIL-12 expression by approximately 25-fold relative to the naked mIL-12 pDNA. There was a significant tumor growth inhibition after repeated injections of mIL-12 pDNA-loaded nanoliposomes. This is the first study on the freeze-drying of a monophase solution method as a simple yet novel technique for the preparation of pDNA-loaded nanoliposomes. Given the ease of preparation method and promising in vitro and in vivo characteristics, this investigation demonstrates advances in pDNA lipid formulation for cancer gene therapy.

Microbial Alpha-Amylase Production: Progress, Challenges and Perspectives.

Alpha-amylase reputes for starch modification by breaking of 1-4 glycosidic bands and is widely applied in different industrial sectors. Microorganisms express unique alpha-amylases with thermostable and halotolerant characteristics dependent on the microorganism's intrinsic features. Likewise, genetic engineering methods are applied to produce enzymes with higher stability in contrast to wild types. As there are widespread application of α-amylase in industry, optimization methods like RSM are used to improve the production of the enzyme ex vivo. This study aimed to review the latest researches on the production improvement and stability of α-amylase.

Investigation of pectin/starch hydrogel as a carrier for oral delivery of probiotic bacteria.

The present study highlights the fabrication of novel food-grade hydrogel particles based on pectin and starch for probiotic colon delivery. Lactobacillus plantarum ATCC:13643 (L. plantarum) cells were encapsulated in pectin/starch hydrogels by extrusion method. Four batches were formulated with different ratios of starch/pectin solutions. Optical and scanning electron microscopy obviously showed the random distribution of L. plantarum throughout the hydrogel network. The viability of encapsulated cells in simulated gastric fluid (SGF) and bile salt solution was significantly higher when compared to nonencapsulated cells. Results demonstrated that encapsulated cells in pectin/starch hydrogels were resistant against adverse conditions of the gastro-intestinal tract and bile salt solution compared to non-encapsulated cells. After sequential exposure to simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) for 2h almost complete death of free cells was observed however the numbers of surviving cells were 5.15 and 6.67 Log CFU/g for pectin and pectin/starch hydrogel, respectively.

Effector diversification within compartments of the Leptosphaeria maculans genome affected by Repeat-Induced Point mutations.

Fungi are of primary ecological, biotechnological and economic importance. Many fundamental biological processes that are shared by animals and fungi are studied in fungi due to their experimental tractability. Many fungi are pathogens or mutualists and are model systems to analyse effector genes and their mechanisms of diversification. In this study, we report the genome sequence of the phytopathogenic ascomycete Leptosphaeria maculans and characterize its repertoire of protein effectors. The L. maculans genome has an unusual bipartite structure with alternating distinct guanine and cytosine-equilibrated and adenine and thymine (AT)-rich blocks of homogenous nucleotide composition. The AT-rich blocks comprise one-third of the genome and contain effector genes and families of transposable elements, both of which are affected by repeat-induced point mutation, a fungal-specific genome defence mechanism. This genomic environment for effectors promotes rapid sequence diversification and underpins the evolutionary potential of the fungus to adapt rapidly to novel host-derived constraints.