Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: An animal study.

AIM: This study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. MATERIALS AND METHODS: Eighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. RESULTS: The average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. CONCLUSION: Metformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

Revolutionizing Infection Control: Harnessing MXene-Based Nanostructures for Versatile Antimicrobial Strategies and Healthcare Advancements.

The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques. Crucial characterization techniques such as XRD, Raman spectroscopy, SEM/TEM, FTIR, XPS, and BET analysis provide insightful structural and functional attributes. The review highlights MXenes' diverse antimicrobial mechanisms, spanning membrane disruption and oxidative stress induction, demonstrating efficacy against bacterial, viral, and fungal infections. Despite translational hurdles, MXene-based nanostructures offer broad-spectrum antimicrobial potential, with applications in drug delivery and diagnostics, presenting a promising path for advancing infection control in global healthcare.

Relationship between body mass index and mortality of burns patients: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the relationship between body mass index (BMI) and mortality of burn patients. A comprehensive, systematic search was conducted in different international electronic databases, such as Scopus, PubMed, Web of Science and Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as "Body mass index", "Burns" and "Mortality" from the earliest to the April 1, 2023. The quality of the studies included in this systematic review was evaluated using the appraisal tool for cross-sectional studies (AXIS tool). Finally, six articles were included in this systematic review and meta-analysis. A total of 16 154 burn patients participated in six studies. Their mean age was 46.32 (SD = 1.99). Of the participants, 71.7% were males. The mean length of hospitalization was 18.80 (SD = 8.08) days, and the average TBSA in burn patients was 38.32 (SD = 2.79) %. Also, the average BMI in burn patients was 27.10 (SD = 1.75). Results found mortality in patients with abnormal BMI (overweight to morbidity BMI) was 0.19 more than normal BMI (ES: 1.19, 95%CI: 0.76-1.87, Z = 0.75, I2 : 71.8%, p = 0.45). Results of linear dose-response showed each 5 kg/m2 increase in BMI was associated with a 5% increase in mortality that was marginally significant (ES: 1.05, 95%CI: 1.00-1.11, Z = 1.99, I2 : 22.2%, p = 0.047). There was a non-linear relationship between levels of BMI and mortality (Prob > χ2 = 0.02). There was an increase in mortality from percentile 10 to 50, although it was not significant (Correlational coefficient: 0.01, p = 0.85). Also, there was an increase in mortality rate from percentile 50 to 90 that was statistically significant (correlational coefficient: 0.06, p = 0.047). Finally, the results of the study indicated BMI can increase the chance of mortality by 0.19, although it was not significant. As a result, more studies are needed to better judge the relationship between BMI and mortality in burn victims.

The consequences of orthodontic extrusion on previously intruded permanent incisors-A retrospective study.

AIM: The aim of this study is to compare the adverse effects that occur after orthodontic extrusion of teeth that have been traumatically intruded with those of similar teeth that have not experienced any trauma. BACKGROUND: The outcome of incisors intrusion can be affected by the patient's age, extent of injury, root development, and malocclusion. Orthodontic extrusion is a potential solution, but it may also cause complications. MATERIALS AND METHODS: A retrospective study of the effects of extrusion of traumatically intruded teeth was carried out. The study group included 21 teeth in 14 patients. The control group included 32 teeth in 10 patients that underwent orthodontic extrusion with no history of trauma. Patients' age, gender, and stage of root development were recorded. The severity of the intrusion was classified as mild (<3 mm), moderate (3-6 mm), and severe (≥7 mm). A comparison of signs of pulp necrosis and root resorptions between the groups was made. RESULTS: The central incisor is the tooth that is most injured in 80.9% of cases. A majority of these incidents involve severe intrusion, which was found in 42.9% of cases. 90% of the traumatized teeth had already lost their vitality prior to orthodontic treatment. Various forms of root resorption were observed in the study group. In the control group, 31.2% of teeth showed signs of external root resorption, but no endodontic intervention was carried out during the follow-up period, as these teeth remained vital. CONCLUSIONS: Following intrusion, there is a high risk for root resorption and pulp necrosis. Orthodontic repositioning should be carried out with caution and mild force to prevent complications. Long-term follow-ups are required to ensure the best possible outcome.

Synthesis of a novel Cu/DPA-MOF/OP/CS hydrogel with high capability in antimicrobial studies.

Today, with the indiscriminate use of antibiotics, we face the resistance of some bacterial strains against some antibiotics. Therefore, it is essential to report and synthesize new compounds with antimicrobial properties. A novel copper/dipicolinic acid-metal-organic framework cross-linked oxidized pectin and chitosan (Cu/DPA-MOF/OP/CS) hydrogel polymer was synthesized under environmental conditions with the controllable process, which uses biodegradable polymer compounds such as pectin and chitosan in its structure. The efficient physicochemical features of the synthesized Cu/DPA-MOF/OP/CS hydrogel using SEM, FT-IR, TGA, BET, XRD, and EDS/mapping were identified and confirmed. The newly synthesized Cu/DPA-MOF/OP/CS hydrogel showed activity against Gram-positive and Gram-negative bacterial strains and fungal species, and significant antibacterial and antifungal properties were observed. In antibacterial activity, the MIC against Gram-positive species was in the range of 16-128 mg/mL, the MIC against Gram-negative species was in the range of 64-256 mg/mL, and the MIC against fungal species was in the range of 128-512 mg/mL. In antimicrobial evaluations, in addition to the MIC test, the MBC test, the MFC test, and the IZD test were performed, and the results were reported. The results were compared with commercial antibiotics in the market. Development of novel nanostructures based on hydrogel polymers with distinctive functionality can affect the performance of these nanostructures in different areas.

The emerging role of 27-hydroxycholesterol in cancer development and progression: An update.

Oxysterols are cholesterol metabolites generated in the liver and other peripheral tissues as a mechanism of removing excess cholesterol. Oxysterols have a wide range of biological functions, including the regulation of sphingolipid metabolism, platelet aggregation, and apoptosis. However, it has been found that metabolites derived from cholesterol play essential functions in cancer development and immunological suppression. In this regard, research indicates that 27-hydroxycholesterol (27-HC) might act as an estrogen, promoting the growth of estrogen receptor (ER) positive breast cancer cells. The capacity of cholesterol to dynamically modulate signaling molecules inside the membrane and particular metabolites serving as signaling molecules are two possible contributory processes. 27-HC is a significant metabolite produced mainly through the CYP27A1 (Cytochrome P450 27A1) enzyme. 27-HC maintains cholesterol balance biologically by promoting cholesterol efflux via the liver X receptor (LXR) and suppressing de novo cholesterol production through the Insulin-induced Genes (INSIGs). It has been demonstrated that 27-HC is able to function as a selective ER regulator. Moreover, enhanced 27-HC production is in favor of the growth of end-stage malignancies in the brain, thyroid organs, and colon, as shown in breast cancer, probably due to pro-survival and pro-inflammatory signaling induced by unbalanced levels of oxysterols. However, the actual role of 27-HC in cancer promotion and progression remains debatable, and many studies are warranted to be performed to unravel the precise function of these molecules. This review article will summarize the latest evidence on the deleterious or beneficial functions of 27-HC in various types of cancer, such as breast cancer, prostate cancer, colon cancer, gastric cancer, ovarian cancer, endometrial cancer, lung cancer, melanoma, glioblastoma, thyroid cancer, adrenocortical cancer, and hepatocellular carcinoma.

Perspectives and Trends in Advanced MXenes-Based Optical Biosensors for the Recognition of Food Contaminants.

Fabricating novel biosensing constructs with high sensitivity and selectivity is highly demanded in food contaminants detection. In this prospect, various nanostructured materials were envisaged to build (bio)sensors with superior sensitivity and selectivity. The desirable biocompatibility, brilliant mechanical strength, ease of surface functionalization, as well as tunable optical and electronic features, portray 2D MXenes as versatile scaffolds for biosensing. In this review, we overviewed the state-of-the-art MXenes-based optical biosensing devices to detect mycotoxins, pesticide residues, antibiotic residues, and food borne-pathogens from foodstuff and environmental matrices. Firstly, the synthesis methods and surface functionalization/modification of MXenes are discussed. Secondly, according to the target analytes, we categorized and presented a detailed account of the newest research progress of MXenes-based optical probes for food contaminants monitoring. The efficiency of all the surveyed probes was assessed on the basis of important factors like response time, detection limit (DL), and sensing range. Lastly, the necessity and requirements for future advances in this emerging MXenes material are also given, followed by challenges and opportunities. We hope that this study will bridge the gap between nanotechnology and food science, offering insights for engineers or scientists in both areas to accelerate the progress of MXenes-based materials for food safety detection.

Placental colonization by Fusobacterium nucleatum is mediated by binding of the Fap2 lectin to placentally displayed Gal-GalNAc.

While the existence of an indigenous placental microbiota remains controversial, several pathogens are known to be involved in adverse pregnancy outcomes. Fusobacterium nucleatum is an oral bacterium that is one of several bacteria associated with preterm birth. Oral fusobacteria translocate to the placenta hematogenously; however, the mechanisms localizing them to the placenta remain unclear. Here, using peanut agglutinin, we demonstrate that the level of Gal-GalNAc (Galß1-3GalNAc; Thomsen Friedenreich antigen) found on trophoblasts facing entering maternal blood rises during gestation and is recognized by the fusobacterial Fap2 Gal-GalNAc lectin. F. nucleatum binding to human and mouse placenta correlates with Gal-GalNAc levels and is reduced upon O-glycanase treatment or with soluble Gal-GalNAc. Fap2-inactivated F. nucleatum shows reduced binding to Gal-GalNAc-displaying placental sections. In a mouse model, intravenously injected Fap2-expressing F. nucleatum, but not a Fap2 mutant, reduces mouse fetal survival by 70%.

Drug delivery and anticancer activity of biosynthesised mesoporous Fe2 O3 nanoparticles.

Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2 O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 µg.ml-1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic-diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti-cancer drug doxorubicin.

Evaluating the Level of Serum IL-23 in Brucellosis Infection by ELISA and Investigating its Relationship in Cases with Failure to Respond to Treatment.

Brucella is belonging to the small immobile gram-negative spore-lacking cocco-bacilli bacteria family that grows in an aerobic environment, it is known as a zoonosis infection named brucellosis. This study was designed to investigate serum values of IL-23 in patient with brucellosis and investigate its relationship with cases with failure to respond to conventional medical therapy. A total of 372 individuals were divided into 2 groups (n=186) as follows: Group A comprising 186 infected participants with brucella (7-80 years-old), these people had not received antibiotics for at least 6 months ago. Group B including the healthy participants. All the participants in both groups were in the same age range. 5 ml blood samples were obtained from the participants intravenously (without anticoagulation substance). The serum level of IL-23 was investigated by ELISA diagnostic kit. The recorded data showed that the levels of IL-23 in the serum samples obtained from group A (143.64 Pg/ml) significantly (P<0.001) increased compared with this value in group B (23.14 Pg/ml). Based on the recorded data in the forms completed by all the participants at the day 0 of the experiment, 44 out of 186 individuals in group A, had experienced Brucellosis attack 2-3 times in spite of receiving medical prescriptions. A hypothesis about the possible immune system disorders in these participants lead us to did the re-sampling following drug administration. Results illustrated failure to respond to conventional medical therapy in patients with low level of serum IL-23.

Identify Breast Cancer Risk Factors Using the Gail Assessment Model in Iraq.

The prevalence of breast cancer (BC) has increased significantly in the last 50 years worldwide. This increase may be because more women today have mammograms and, as a result, are more known to have cancers. At the same time, the theory is growing that many other factors contribute to the increase in cancer rates. The current study tried applying the Gail assessment model to identify hormonal and familial risk factors that may be important for BC in Iraq. Patients aged 30 years and over with all known risk factors for BC were selected for the study group. The selected patients were divided into two groups. Group 1: Patients diagnosed with non-proliferative lesions who have had a breast biopsy performed at least three years before; Group 2: Controlled patients. The individual risk of BC for patients in groups 1 and 2 was calculated using the Gale model. In addition to groups 1 and 2, we identified two other groups. Group 3: Groups 1 and 2 of patients without BC at the end of the 3-year follow-up period; Group 4: Patients who have undergone BC surgery. Multiple regression tests assessed all known risk factors in groups 3 and 4 to determine the risk factors for the development of BC in Iraq. The results show that Gail's assessment model is a reliable example of calculating the risk of developing BC. The model results show that the significant risk factor for BC in Iraq is not hormonal but genetic or familial. Current research also shows that the risk of developing BC increases significantly with age. It was concluded that there are genetic factors, and the risk of developing BC increases with age, but hormonal features do not cause a significant increase in risk. Identifying risk factors in causing disease in the community makes it possible to prepare codified plans to control and treat the disease.

Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System.

Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.

Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression.

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice, hematogenous F. nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels. We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc. Intravascularly inoculated Fap2-expressing F. nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization. Inoculation with F. nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment. Thus, targeting F. nucleatum or Fap2 might be beneficial during treatment of breast cancer.

Tumor Targeting by Fusobacterium nucleatum: A Pilot Study and Future Perspectives.

Colorectal adenocarcinoma (CRC) is a common tumor with high mortality rates. Interestingly, CRC was found to be colonized by the oral anaerobic bacteria Fusobacterium nucleatum, which accelerates tumor progression and enables immune evasion. The CRC-specific colonization by fusobacteria is mediated through the recognition of tumor displayed Gal-GalNAc moieties by the fusobacterial Fap2 Gal-GalNAc lectin. Here, we show high Gal-GalNAc levels in additional adenocarcinomas including those found in the stomach, prostate, ovary, colon, uterus, pancreas, breast, lung, and esophagus. This observation coincides with recent reports that found fusobacterial DNA in some of these tumors. Given the tumorigenic role of fusobacteria and its immune evasion properties, we suggest that fusobacterial elimination might improve treatment outcome of the above tumors. Furthermore, as fusobacteria appears to specifically home-in to Gal-GalNAc-displaying tumors, it might be engineered as a platform for treating CRC and the above common, lethal, adenocarcinomas.

Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc.

Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.

Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.

Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.

Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells.

Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI.