The dual interaction of antimicrobial peptides on bacteria and cancer cells; mechanism of action and therapeutic strategies of nanostructures.

Microbial infection and cancer are two leading causes of global mortality. Discovering and developing new therapeutics with better specificity having minimal side-effects and no drug resistance are of an immense need. In this regard, cationic antimicrobial peptides (AMP) with dual antimicrobial and anticancer activities are the ultimate choice. For better efficacy and improved stability, the AMPs available for treatment still required to be modified. There are several strategies in which AMPs can be enhanced through, for instance, nano-carrier application with high selectivity and specificity enables researchers to estimate the rate of drug delivery to a particular tissue. In this review we present the biology and modes of action of AMPs for both anticancer and antimicrobial activities as well as some modification strategies to improve the efficacy and selectivity of these AMPs.

The correlation between IgM and IgG antibodies with blood profile in patients infected with severe acute respiratory syndrome coronavirus.

OBJECTIVES: This study aimed to determine the levels of IgM and IgG antibody response to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 in coronavirus disease 2019 (COVID-19) patients with different disease severity. METHODS: IgM and IgG antibody levels were evaluated via enzyme-linked immunosorbent assay (ELISA). In total, 100 patients with confirmed SARS-CoV-2 infection were enrolled in this study and viral RNA was detected by using Real-time PCR technique. Clinical and laboratory data were collected and analyzed after hospital admission for COVID-19 and two months post-admission. RESULTS: The level of anti-SARS-CoV-2 antibody IgG was significantly higher in the severe patients than those in moderate and mild groups, 2 months after admission. Also, level of IgG was positively associated with increased WBC, NUT and LYM counts in sever than mild or moderate groups after admission to hospital. CONCLUSION: Our findings suggested that patients with severe illness might experience longer virus exposure times and have a stronger antibody response against viral infection. Thus, they have longer time immunity compared with other groups.

The elevation of S100B and downregulation of circulating miR-602 in the sera of ischemic stroke (IS) patients: the emergence of novel diagnostic and prognostic markers.

Ischemic stroke (IS) is a major cause of mortality and disability. However, no reliable prognostic or diagnostic biomarker has been utilized to date. Here, we have evaluated the serum S100B concentration and miR-602 expression as potential biomarkers for IS. Fifty-two IS patients and 52 age- and sex-matched healthy volunteers were enrolled. Blood samples were collected from all patients at the time of admission, 24 and 48 h later, at the time of discharge, and 3 months later. Real-time (RT) PCR was used to measure the serum level of miR602. We also measured the serum concentration of S100B using ELISA. As compared with healthy subjects, IS patients had a higher level of serum S100B and lower serum miR-602. ROC curve analyses revealed that miR-602 (AUC = 0.8168; P < 0.0001) and S100B (AUC = 0.8699; P < 0.0001) had acceptable ability to differentiate between IS patients from healthy subjects. Furthermore, serum S100B was a reliable predictor of the survival outcome at 3 months (P = 0.021). The expression of miR-602 was significantly higher in patients with bigger NIHSS scores. The lower levels of miR-602 and higher concentration of S100B in the sera of IS patients could be associated with clinically significant diagnostic utilities. S100B could be also introduced as a reliable prognostic marker for stroke and implemented in future research.

A Case of Fungus Ball-Type Pansinusitis Due to Fusarium proliferatum.

Incidence of fungal sinusitis due to the genus Fusarium has increased during the last two decades. We report a case of fungus ball sinusitis with multiple sinuses involvement in an Iranian 21-year-old woman. The patient was diagnosed as having a fungus ball-type sinusitis in computed tomography scan. The sinus biopsy revealed fungal structures on histopathological and direct microscopic examinations and a Fusarium species arose in culture. Partial sequencing of the translation elongation factor 1-alpha identified the isolate as F. proliferatum. Removal of all lesions by endoscopic surgery resulted in a favorable outcome. To the best of our knowledge, this is the first case of F. proliferatum-associated fungus ball which involved multi-sinus and highlights the efficiency of molecular methods for discrimination of fungal agents involved.

Prooxidant-antioxidant balance and hs-CRP in patients with beta-thalassemia major.

BACKGROUND: Beta-thalassemia major is one of the most frequent hemoglobinopathies in the world. This is a study on the levels of prooxidant-antioxidant balance (PAB) that can measure the pro-oxidant burden and the anti-oxidant capacity simultaneously in one assay, giving a redox index, as well as an assessment of high-sensitivity C-reactive protein (hs-CRP) in patients with beta-thalassemia major. It also determines the impact both on kidney function tests. METHODS: Ninety subjects with beta-thalassemia major (betaTM) and 90 more healthy subjects as the control group were enrolled in the study. Laboratory parameters, serum hs-CRP, and the novel assay of prooxidant-antioxidant balance were measured. RESULTS: Biochemical and hematological variables, except MCHC, were significantly decreased in patients. Ferritin (p < 0.001) and PAB (p < 0.001) values were statistically increased in patients, whereas hs-CRP (p > 0.05) did not significantly increase in patients. Spearman's correlation univariate analysis showed no significant correlation between PAB with hs-CRP or ferritin. However, there was a significant statistical correlation between hs-CRP with creatinine and triglycerides. Also we found a slight and negative correlation between high-density lipoprotein cholesterol, hemoglobin, and hemotocrit with inflammatory factor. CONCLUSIONS: Briefly, we found higher levels of PAB values and a slight increase in hs-CRP concentration in patients, which may be involved in the pathological consequences of beta-thalassemia major and contribute to the gradual development of injury to the organs.

A successful treatment of rhinocerebral mucormycosis due to Rhizopus oryzae.

Mucormycosis is an invasive fungal infection caused by filamentous fungi of the Mucoraceae family. The genera most commonly responsible are Mucor or Rhizopus. The disease occurs mostly in association with diabetic ketoacidosis. Mucormycosis has an extremely high death rate even when aggressive surgery is done. Death rates range from 25-85% depending on the body area involved. A case of rhinocerebral mucormycosis in a 65-year-old diabetic male patient typically presenting as headache, especially in parietal and frontal lobes, with nose and left eye discharge. After clinical and laboratory examination, mucormycosis was diagnosed, and Rhizopus oryzae was isolated. Systemic therapy with amphotericin B administered intravenously then replaced by posaconazole by a combination of aggressive surgery. The patient was treated and followed up for one year. We emphasize the importance of early detection and aggressive treatment in the management of this fatal disease.

Designing trauma registry system using a logical framework approach.

While trauma registries provide the mechanisms to collect comprehensive, timely and accurate data related to the injuries and evaluate trauma care systems, they have not been established in most developing countries. On the other hand, in complex projects that have large aims, a logical framework approach (LFA) can help summarize and describe the multiple branches of the project systematically, and elucidate the main goals, extensive objectives, activities and expected outcomes. Therefore a LFA can be used to design and guide trauma registry project management, to integrate the cultural, clinical and capacity variations among countries; and to ensure early alignment of the project's design and evaluation.

Comparing Predictive Utility of Head Computed Tomography Scan-Based Scoring Systems for Traumatic Brain Injury: A Retrospective Study.

This study compared the predictive utility of Marshall, Rotterdam, Stockholm, Helsinki, and NeuroImaging Radiological Interpretation System (NIRIS) scorings based on early non-contrast brain computed tomography (CT) scans in patients with traumatic brain injury (TBI). The area under a receiver operating characteristic curve (AUROC) was used to determine the predictive utility of scoring systems. Subgroup analyses were performed among patients with head AIS scores > 1. A total of 996 patients were included, of whom 786 (78.9%) were males. In-hospital mortality, ICU admission, neurosurgical intervention, and prolonged total hospital length of stay (THLOS) were recorded for 27 (2.7%), 207 (20.8%), 82 (8.2%), and 205 (20.6%) patients, respectively. For predicting in-hospital mortality, all scoring systems had AUROC point estimates above 0.9 and 0.75 among all included patients and patients with head AIS > 1, respectively, without any significant differences. The Marshall and NIRIS scoring systems had higher AUROCs for predicting ICU admission and neurosurgery than the other scoring systems. For predicting THLOS ≥ seven days, although the NIRIS and Marshall scoring systems seemed to have higher AUROC point estimates when all patients were analyzed, five scoring systems performed roughly the same in the head AIS > 1 subgroup.

Association between Pro-oxidant-Antioxidant balance and high-sensitivity C-reactive protein in type 2 diabetes mellitus: A Study on Postmenopausal Women.

INTRODUCTION: Oxidative stress known as a predictive marker for cardiovascular and metabolic diseases could be measured through pro-oxidant antioxidant balance (PAB). The present study aimed to evaluate PAB and its association with high-sensitivity C-reactive protein (hs-CRP) in the serum of postmenopausal women with diabetes mellitus. METHODS: In this case-control study, 99 diabetic and 100 healthy postmenopausal women without diabetes mellitus were recruited. Serum PAB values, hs-CRP, lipid profile, insulin, and vitamin D levels were measured. Moreover, insulin resistance (HOMA-IR, HOMA-ß and QUICKI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI) were calculated. RESULTS: Serum PAB, hs-CRP, insulin resistance, HOMA-ß, QUICKI, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels were significantly higher in the postmenopausal women with diabetes mellitus, while there was no significant difference in the total cholesterol (TC), serum insulin, WC, WHR, WHtR and vitamin D levels between the groups. Pearson correlation coefficient showed that HDL-C and insulin levels were directly correlated with serum PAB. Also, there was a significant direct relationship between LDL-C and insulin levels and hs-CRP. There was no meaningful relationship between serum insulin and vitamin D levels and other assessed parameters. Backward logistic regression showed a positive relationship between diabetes mellitus and serum PAB and an inverse relationship with serum HDL levels. CONCLUSIONS: Serum PAB, hs-CRP concentration, and lipid profile were significantly different between postmenopausal women with and without diabetes mellitus. These differences may contribute to the development of coronary complications.

Association between hypertension and clinical outcomes in COVID-19 patients: a case-controlled study.

The outbreak of coronavirus disease 2019 (COVID-19), which was originated from a severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) infection, has become an international public health emergency. The aim of this study was to assess the clinical symptoms and physical findings in both hypertensive and nonhypertensive patients infected with COVID-19. Methods: A retrospective observational case-control study with diagnosis of COVID-19 by laboratory-confirmed test was conducted on 280 consecutive unselected patients. This was a single-center study. The demographics, laboratory, and clinical findings data were extracted from the hospital registry database. Results: Of our 280 patients in the study, there were 149 men (53%) and 138 (50%) were older than 60 years (mean=67.75), and also 50 in-hospital deaths occurred (mortality rate, 17%). Total 19(6.9%) were taking opioid, and smoking. There were no significant differences in the rate of fever, cough, sputum production, gastrointestinal symptoms, myalgia, and headache in the both hypertensive and nonhypertensive groups. The prevalence of underlying diseases was significantly higher in older patients in comparison with younger ones (P=0<0.05), COVID-19 mortality was noticed to be higher among hypertensive patients as compared with nonhypertensive patients (P=0<0.05). Conclusion: Hypertension is associated with a poor prognosis and higher mortality among COVID-19 patients. Optimizing blood pressure is essential during the management of COVID-19. Our research implies the importance of early care and education of old patient with hypertension and other comorbidities.

Synovial fluid adenosine deaminase and high-sensitivity C-reactive protein activity in differentiating monoarthritis.

It is proposed that synovial fluid biomarkers may help in differentiating the type of arthritis. The aim of study is to determine whether synovial fluid adenosine deaminase (ADA) and high-sensitivity C-reactive protein (hs-CRP) can be useful in this regard. A total of 75 patients with knee monoarthritis that were admitted in Shahid Beheshti Kashan hospital in 2009 included in the study. There were 18 rheumatoid arthritis, 13 crystal-induced arthritis, 3 septic arthritis and 41 osteoarthritis. Inflammatory arthritis was diagnosed if more than 2,000 white blood cells existed in per milliliter of the synovial fluid. There was statistically significant difference in mean synovial fluid ADA and hs-CRP concentration between inflammatory (26.06 ± 8.96 IU/l, 12.72 ± 9.25 µg/ml) and non-inflammatory arthritis (14.8 ± 2.79 IU/l, 2.36 ± 2.7 µg/ml) (P values = 0.00, 0.00). There was statistically significant difference in mean synovial fluid ADA and hs-CRP concentration when rheumatoid arthritis (23.77 ± 4.58 IU/l, 10.47 ± 6.99 µg/ml), crystal-induced arthritis (22.76 ± 3.65 IU/l, 14.37 ± 11.58 µg/ml) and septic arthritis (49.66 ± 8.96 IU/l, 18.25 ± 5.37 µg/ml) were compared with osteoarthritis (14.58 ± 2.63 IU/l, 1.91 ± 1.31 µg/ml) (All P values = 0.00). There was statistically significant difference in mean synovial fluid ADA concentration between septic and rheumatoid arthritis and also between septic arthritis and crystal-induced arthritis (P values = 0.00, 0.00). This study showed that synovial fluid ADA and hs-CRP can properly differentiate inflammatory from non-inflammatory arthritis. Synovial fluid ADA is a useful marker in differentiating septic from rheumatoid and crystal-induced arthritis.

Expression and Prognostic Significance of Stem Cell Marker CD133 in Survival Rate of Patients with Colon Cancer.

INTRODUCTION: Today, colon cancer is one of the most common types of gastrointestinal cancer worldwide. CD133 as a known cancer stem cell marker has been found effective in cell proliferation and differentiation in various cancers, including colon cancer. We aimed to investigate the relationship between CD133 expression in colon cancer with prognostic factors and survival rate of patients with colon cancer by immunohistochemistry. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue was taken from patients with colon cancer. Histopathology examination was done using hematoxylin and eosin staining. Immunohistochemistry was performed to determine CD133 expression. Association between CD133 expression and clinicopathological profile was then assessed. RESULTS: There was a statistically significant association between CD133 protein expression and sex , cancer stage, and lymphatic invasion (p = 0.044, p = 0.131, and p = 0.002, respectively). However, no significant correlation was identified between CD133 expression and other factors, including age of patients with colorectal cancer (CRC) (p = 0.267), tumor location (p = 0.494), tumor differentiation grade (p = 0.263), neural tissue invasion, and 5-year survival (p = 0.054). CONCLUSION: CD133 is a useful predictive or prognostic biomarker for CRC in clinical assessment and may serve as a potential therapeutic target for CRC.

The Effect of Irisin on Proliferation, Apoptosis, and Expression of Metastasis Markers in Prostate Cancer Cell Lines.

INTRODUCTION: Irisin is a newly discovered myokine released from skeletal muscle during exercise. The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play a key role in the metastatic process via degrading extracellular matrix. The aim of this study was to investigate the effect of irisin on expression of metastatic markers MMP2 and MMP9 and induced apoptosis in human prostate cancer cells. METHODS: In this study, we examined the effect of different concentrations of irisin on induced apoptosis and cell viability of two cell lines, LNCaP and DU-145, by using flow cytometry and MTT assay, respectively. The expression of MMP2 and MMP9 genes was also analyzed by real-time PCR after irisin treatment. Data were analyzed using the comparative cycle threshold 2-∆∆Ct method. RESULTS: Cell viability was reduced in both LNCaP and DU-145 cell lines at different concentrations of irisin. However, this decreased cell viability was strongly significant (p < 0.05) only at 5 and 10 nM concentrations of irisin in the LNCaP cell line. Furthermore, irisin could induce apoptosis in both cell lines at a concentration of 10 nM compared to 5 nM. Real-time PCR results also demonstrated a decreased expression in MMP2 and MMP9 genes in a concentration-dependent manner in both cell lines. CONCLUSION: These results showed the anticancer effects of irisin on cell viability of both LNCaP and DU-145 cell lines and also on the expression of MMP2 and MMP9 genes occurred in a dose- and time-dependent manner.

Molecular and Clinical Investigation of COVID-19: From Pathogenesis and Immune Responses to Novel Diagnosis and Treatment.

The coronavirus-related severe acute respiratory syndrome (SARS-CoV) in 2002/2003, the Middle East respiratory syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 severe acute respiratory syndrome-2 (SARS-CoV-2) negatively affected the national health systems worldwide. Different SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and recently Omicron (B.1.1.529), have emerged resulting from the high rate of genetic recombination and S1-RBD/S2 mutation/deletion in the spike protein that has an impact on the virus activity. Furthermore, genetic variability in certain genes involved in the immune system might impact the level of SARS-CoV-2 recognition and immune response against the virus among different populations. Understanding the molecular mechanism and function of SARS-CoV-2 variants and their different epidemiological outcomes is a key step for effective COVID-19 treatment strategies, including antiviral drug development and vaccine designs, which can immunize people with genetic variabilities against various strains of SARS-CoV-2. In this review, we center our focus on the recent and up-to-date knowledge on SARS-CoV-2 (Alpha to Omicron) origin and evolution, structure, genetic diversity, route of transmission, pathogenesis, new diagnostic, and treatment strategies, as well as the psychological and economic impact of COVID-19 pandemic on individuals and their lives around the world.

Survivin c.-31G>C (rs9904341) gene transversion and urinary system cancers risk: a systematic review and a meta-analysis.

AIM: To investigate the possible association between survivin c.-31G>C (rs9904341) gene polymorphism and urinary system cancers by a meta-analysis approach. METHODS: Standard electronic literature databases were searched to find eligible studies. The odds ratios (ORs) with 95% CIs were estimated to find the associations possibility. RESULTS: Overall meta-analysis revealed significant associations between c.-31G>C transversion and risk of urinary tract cancers in dominant (OR: 1.34; 95% CI: 1.02-1.75; p = 0.035), recessive (OR: 1.52; 95% CI: 1.33-1.74; p < 0.001) and homozygote codominant (OR: 1.90; 95% Cl: 1.37-2.62; p < 0.001) genetic models. CONCLUSION: The c.-31G>C transversion might be a risk factor for urinary system cancers. However, more articles with different ethnicities will help to obtain a more accurate conclusion.

Association of Some High-Risk Mucosal Types of Human Papillomavirus with Cutaneous Squamous Cell Carcinoma in an Iranian Population.

BACKGROUND & OBJECTIVE: Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer that may be caused by Human papillomavirus (HPV), especially in immunosuppressed patients. However, the role of the mucosal types of HPV in SCC patients with normal immunity has not been extensively confirmed. The aim of this study was to investigate the association of some high-risk mucosal types of HPV with cutaneous SCC in an Iranian population. METHODS: Sixty-five formalin-fixed, paraffin-embedded tissue specimens with a diagnosis of cutaneous SCC as the case group and sixty-five healthy skin specimens as the control group were included in our case-control study. Genomic DNA was extracted from tissue samples and then PCR was used for the detection of HPV genotypes by a commercial kit. RESULTS: Our data revealed that 6 out of 65 SCC samples (9.2%) were infected by high-risk mucosal types of HPV whereas none of the 65 control samples were infected by the mentioned HPVs. Statistical analysis showed a significant association between these types of HPV infection and SCC risk in our studied population (P=0.028). CONCLUSION: These findings suggested that some high-risk mucosal types of HPV are significant risk factors for cutaneous SCC.

Apolipoproteins A1, B, and other prognostic biochemical cardiovascular risk factors in patients with beta-thalassemia major.

OBJECTIVES: The occurrence of cardiac iron deposition is one of the late effect of iron over load which causes cardiovascular disease (CVD) in patients who are affected by beta-thalassemia major. Evaluation of some cardiovascular risk factors plays a crucial role in prediction and prevention of CVD. SUBJECTS AND METHODS: This study consisted of 70 young adult subjects with beta-thalassemia major (beta-TM) (aged <30 years) and 71 age- and sex-matched healthy subjects as control group in the range of 20-30 years. Hematological and biochemical laboratory parameters including apolipoprotein (Apo)A1 and ApoB, oxidative stress biomarker pro-oxidant-antioxidant balance (PAB), homocysteine, serum high-sensitivity C-reactive protein (hs-CRP), and lipid profile were evaluated. RESULTS: ApoA1, ApoB, lipid profiles, and homocysteine were significantly decreased in patients group (P < 0.001); however, very low-density lipoprotein and also mean corpuscular hemoglobin concentration (P > 0.05) were different. Some elements included ferritin (P < 0.001), PAB (P < 0.001), and ApoB/apoA1 ratio (P < 0.05) statistically increased in patients, whereas hs-CRP (P > 0.05) was not significantly different in study groups. Exception of high-density lipoprotein (P > 0.05), other lipid profiles, and apoB had a negative meaningful correlation with PAB (P < 0.05). Likewise, apoA1, apoB, apoB/A1 ratio with apoB and homocysteine showed a strong correlation (P < 0.05). We did not find a slight correlation between apoB/A1 ratio in the company of oxidative stress marker PAB (r = -0.366; P = 0.086). We found a statistical correlation between apoB/A1 and homocysteine (P < 0.05). DISCUSSION: Higher level of some risk factors like PAB values, apoB/A1 ratio concentration, and lipid profiles is able to involve in the prognostic pathological consequences in patients with beta-thalassemia major. Even so, they contribute toward the gradual development of CVD.

A Review on Iron Chelators in Treatment of Iron Overload Syndromes.

Iron chelation therapy is used to reduce iron overload development due to its deposition in various organs such as liver and heart after regular transfusion. In this review, different iron chelators implicated in treatment of iron overload in various clinical conditions have been evaluated using more up-to-date studies focusing on these therapeutic agents. Deferoxamine, Deferiprone and Deferasirox are the most important specific US FDA-approved iron chelators. Each of these chelators has their own advantages and disadvantages, various target diseases, levels of deposited iron and clinical symptoms of the afflicted patients which may affect their selection as the best modality. Taken together, in many clinical disorders, choosing a standard chelator does not have an accurate index which requires further clarifications. The aim of this review is to introduce and compare the different iron chelators regarding their advantages and disadvantages, usage dose and specific applications.

Occult hepatitis C virus infection in Iranian hemodialysis patients.

BACKGROUND: Occult hepatitis C virus (HCV) infection is defined as the presence of HCV-RNA in liver or peripheral blood mononuclear cells (PBMCs) in the absence of detectable hepatitis C antibody (anti-HCV) or HCV-RNA in the serum. Low concentrations of HCV-RNA may be detected in PBMCs of hemodialysis (HD) patients and this could have a great impact on the management of HD patients. OBJECTIVES: The aim of this study was to detect the occult HCV infection in Iranian HD patients. PATIENTS AND METHODS: A total of 70 anti-HCV negative HD patients from three dialysis units in Tehran, Iran were included in this study. In these cases, presence of HCV-RNA in plasma samples was tested by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). In cases with negative anti-HCV and plasma HCV-RNA, genomic HCV-RNA was checked in PBMC specimens by RT-nested PCR. RESULTS: Seventy anti-HCV negative HD patients were enrolled in the study. 32.85% and 1.43% of cases had elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) respectively. 7.14% of patients had elevated levels of both ALT and AST. HCV-RNA was negative in plasma samples of all anti-HCV negative HD subjects. The genomic HCV-RNA was not detected in any PBMC samples of HD cases with negative anti-HCV and plasma HCV-RNA. CONCLUSIONS: Occult HCV infection was not detected in our HD patients despite of elevated levels of liver enzymes in some participants. Further studies involving larger number of HD patients are required to elucidate the rate of occult HCV infection in HD cases.