Nanoliposomes as nonviral vectors in cancer gene therapy.

Nonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off-targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions.

Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors.

Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.

Biological landscape and nanostructural view in development and reversal of oxaliplatin resistance in colorectal cancer.

The treatment of cancer patients has been mainly followed using chemotherapy and it is a gold standard in improving prognosis and survival rate of patients. Oxaliplatin (OXA) is a third-platinum anti-cancer agent that reduces DNA synthesis in cancer cells to interfere with their growth and cell cycle progression. In spite of promising results of using OXA in cancer chemotherapy, the process of drug resistance has made some challenges. OXA is commonly applied in treatment of colorectal cancer (CRC) as a malignancy of gastrointestinal tract and when CRC cells increase their proliferation and metastasis, they can obtain resistance to OXA chemotherapy. A number of molecular factors such as CHK2, SIRT1, c-Myc, LATS2 and FOXC1 have been considered as regulators of OXA response in CRC cells. The non-coding RNAs are able to function as master regulator of other molecular pathways in modulating OXA resistance. There is a close association between molecular mechanisms such as apoptosis, autophagy, glycolysis and EMT with OXA resistance, so that apoptosis inhibition, pro-survival autophagy induction and stimulation of EMT and glycolysis can induce OXA resistance in CRC cells. A number of anti-tumor compounds including astragaloside IV, resveratrol and nobiletin are able to enhance OXA sensitivity in CRC cells. Nanoparticles for increasing potential of OXA in CRC suppression and reversing OXA resistance have been employed in cancer chemotherapy. These subjects are covered in this review article to shed light on molecular factors resulting in OXA resistance.

The Effect of Culturally Appropriate Self-Care Intervention on Health Literacy, Health-Related Quality of Life and Glycemic Control in Iranian Patients with Type 2 Diabetes: A Controlled Randomized Clinical Trial.

Background: Cultural and language differences are necessary factors for diabetes management and self-care education programs in patients suffering from diabetes. This study aims to investigate the effectiveness of culture-based self-care intervention on health literacy, quality of life, and glycemic parameters in patients with type 2 diabetes. Materials and Methods: This randomized clinical trial has been carried out in selected centers in Darreh Shahr, Iran; 80 participants were randomly assigned into intervention and control groups. The intervention group received an educational program for 6 sessions twice a week, but the control group only received routine services. Data were collected using health literacy and life quality scales for diabetic patients, which were completed by both groups before, immediately after, and 3 months after the intervention; hemoglobin A1C (HbA1c) was checked before and 3 months after the intervention. SPSS software was also analyzed data using χ2, Fisher's exact, independent t, and repeated measures analysis of variance tests. Results: There were no significant differences between the 2 groups before the study (p >0.05) goes forward. But, mean scores of health literacy (F2,40 = 5.61, p =0.007), quality of life (F2, 40 = 4.09, p =0.01), and HbA1c levels (t, 39 = 6. 91, p <0.001) have shown significant differences between the 2 groups immediately and 3 months after the intervention have been applied. Conclusions: Culturally appropriate intervention should be offered as a part of the nurse' care program for diabetic to control HbA1c, and improve their life quality and health literacy.

Biological and therapeutic viewpoints towards role of miR-218 in human cancers: Revisiting molecular interactions and future clinical translations.

Understanding the exact pathogenesis of cancer is difficult due to heterogenous nature of tumor cells and multiple factors that cause its initiation and development. Treatment of cancer is mainly based on surgical resection, chemotherapy, radiotherapy and their combination, while gene therapy has been emerged as a new kind of therapy for cancer. Post-transcriptional regulation of genes has been of interest in recent years and among various types of epigenetic factors that can modulate gene expression, short non-coding RNAs known as microRNAs (miRNAs) have obtained much attention. The stability of mRNA decreases by miRNAs to repress gene expression. miRNAs can regulate tumor malignancy and biological behavior of cancer cells and understanding their function in tumorigenesis can pave the way towards developing new therapeutics in future. One of the new emerging miRNAs in cancer therapy is miR-218 that increasing evidence highlights its anti-cancer activity, while a few studies demonstrate its oncogenic function. The miR-218 transfection is promising in reducing progression of tumor cells. miR-218 shows interactions with molecular mechanisms including apoptosis, autophagy, glycolysis and EMT, and the interaction is different. miR-218 induces apoptosis, while it suppresses glycolysis, cytoprotective autophagy and EMT. Low expression of miR-218 can result in development of chemoresistance and radio-resistance in tumor cells and direct targeting of miR-218 as a key player is promising in cancer therapy. LncRNAs and circRNAs are nonprotein coding transcripts that can regulate miR-218 expression in human cancers. Moreover, low expression level of miR-218 can be observed in human cancers such as brain, gastrointestinal and urological cancers that mediate poor prognosis and low survival rate.

Biological functions and molecular interactions of Wnt/ß-catenin in breast cancer: Revisiting signaling networks.

Changes in lifestyle such as physical activity and eating habits have been one of the main reasons for development of various diseases in modern world, especially cancer. However, role of genetic factors in initiation of cancer cannot be ignored and Wnt/ß-catenin signaling is such factor that can affect tumor progression. Breast tumor is the most malignant tumor in females and it causes high mortality and morbidity around the world. The survival and prognosis of patients are not still desirable, although there have been advances in introducing new kinds of therapies and diagnosis. The present review provides an update of Wnt/ß-catenin function in breast cancer malignancy. The upregulation of Wnt is commonly observed during progression of breast tumor and confirms that tumor cells are dependent on this pathway Wnt/ß-catenin induction prevents apoptosis that is of importance for mediating drug resistance. Furthermore, Wnt/ß-catenin signaling induces DNA damage repair in ameliorating radio-resistance. Wnt/ß-catenin enhances proliferation and metastasis of breast tumor. Wnt/ß-catenin induces EMT and elevates MMP expression. Furthermore, Wnt/ß-catenin participates in tumor microenvironment remodeling and due to its tumor-promoting factor, drugs for its suppression have been developed. Different kinds of upstream mediators Wnt/ß-catenin signaling in breast cancer have been recognized that their targeting is a therapeutic approach. Finally, Wnt/ß-catenin can be considered as a biomarker in clinical trials.

Antimicrobial resistance, virulence factors, and genotypes of Pseudomonas aeruginosa clinical isolates from Gorgan, northern Iran.

Pseudomonas aeruginosa is an important nosocomial pathogen with a capacity of resistance to multiple antibiotics and production of various extracellular and cell-associated virulence factors that clearly contribute to its pathogenicity. The objective of this study was to investigate the antibiotic susceptibility, virulence factors, and clonal relationship among clinical isolates of P. aeruginosa. Different clinical specimens from hospitalized patients were investigated for P. aeruginosa. Susceptibility of the isolates was evaluated by disc diffusion and broth microdilution methods, as described by the Clinical and Laboratory Standards Institute (CLSI) guideline. A total of 97 P. aeruginosa isolates were recovered from clinical specimens. The percentage of isolates resistant to antimicrobials was imipenem 25.77%, meropenem 15.46%, gentamicin 16.49%, tobramycin 15.46%, amikacin 16.49%, ciprofloxacin 20.61%, levofloxacin 24.74, ceftazidime 20.61%, piperacillin 15.46%, piperacillin/tazobactam 12.37%, colistin 9.27%, and polymyxin B 11.34%. Of isolates, 87.62% possessed ß-hemolytic activity, 78.35% lecithinase, 59.8% elastase, 37.11% DNase, and 28.86% twitching motility. The frequency of virulence genes in isolates was lasB 82.47%, plcH 82.47%, exoA 58.76%, exoS 56.7%, and pilA 10.3%. ERIC-PCR typing clustered P. aeruginosa isolates to 19 common types (CT1-CT19) containing isolates from different hospitals and 43 single types (ST1-ST43). Colistin and polymyxin B were the most effective agents against the majority of P. aeruginosa isolates, emphasizing the effort to maintain their antibacterial activity as last-line therapy. The frequency of some virulence factors and genes was noticeably high, which is alarming. In addition, more effective strategies and surveillance are necessary to confine and prevent the inter-hospital and/or intra-hospital dissemination of P. aeruginosa between therapeutic centers.

Spatial patterning of occupational stress and its related factors in Iranian critical care nurses using a hierarchical Bayesian technique.

BACKGROUND: In each community, health problems' patterns and geographical changes are of prime importance to determine high and low-risk areas. OBJECTIVES: This study aimed to investigate the Spatial patterning of occupational stress and its related factors in Iranian critical care nurses using a hierarchical Bayesian techniqueMETHODS:The current research was a cross-sectional descriptive-analytical study. The data includes the number of critical care unit nurses who show a high stress level based on a questionnaire. We used variables such as age, gender, collaboration status, working time, marital status, clinical experience, education, supervisor support, stress score, and working on holiday days for this study. The survey participants had to be at least 18 years old, a registered nurse, and working in the intensive care unit (ICU). OpenBUGS version 3.2.3 was used to implement the Bayesian hierarchical Poisson model and find partial patterning of occupational stress and its related factors. RESULTS: The final sample size was 17414 nurses. The overall prevalence of occupational stress in ICU nurses was estimated at 70%. The lowest and highest prevalence was 65.8% in the North Khorasan province and 75.2% in Golestan province. Occupational stress had a statistically significant association with collaboration status, but with demographic variables, shift work, supportive supervisor, and working on holidays had no statistically significant association. CONCLUSIONS: According to the findings, it is necessary to eliminate or reduce job stress and increase efficiency in Iranian nurses, encourage teamwork and collaboration as an essential element of a healthy workplace environment.

STAT3-EMT axis in tumors: Modulation of cancer metastasis, stemness and therapy response.

Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis of tumor cells and their spread to various organs and tissues of body, providing undesirable prognosis. In addition to migration, EMT increases stemness and mediates therapy resistance. Hence, pathways involved in EMT regulation should be highlighted. STAT3 is an oncogenic pathway that can elevate growth rate and migratory ability of cancer cells and induce drug resistance. The inhibition of STAT3 signaling impairs cancer progression and promotes chemotherapy-mediated cell death. Present review focuses on STAT3 and EMT interaction in modulating cancer migration. First of all, STAT3 is an upstream mediator of EMT and is able to induce EMT-mediated metastasis in brain tumors, thoracic cancers and gastrointestinal cancers. Therefore, STAT3 inhibition significantly suppresses cancer metastasis and improves prognosis of patients. EMT regulators such as ZEB1/2 proteins, TGF-ß, Twist, Snail and Slug are affected by STAT3 signaling to stimulate cancer migration and invasion. Different molecular pathways such as miRNAs, lncRNAs and circRNAs modulate STAT3/EMT axis. Furthermore, we discuss how STAT3 and EMT interaction affects therapy response of cancer cells. Finally, we demonstrate targeting STAT3/EMT axis by anti-tumor agents and clinical application of this axis for improving patient prognosis.

Therapeutic potential of AMPK signaling targeting in lung cancer: Advances, challenges and future prospects.

Lung cancer (LC) is a leading cause of death worldwide with high mortality and morbidity. A wide variety of risk factors are considered for LC development such as smoking, air pollution and family history. It appears that genetic and epigenetic factors are also potential players in LC development and progression. AMP-activated protein kinase (AMPK) is a signaling pathway with vital function in inducing energy balance and homeostasis. An increase in AMP:ATP and ADP:ATP ratio leads to activation of AMPK signaling by upstream mediators such as LKB1 and CamKK. Dysregulation of AMPK signaling is a common finding in different cancers, particularly LC. AMPK activation can significantly enhance LC metastasis via EMT induction. Upstream mediators such as PLAG1, IMPAD1, and TUFM can regulate AMPK-mediated metastasis. AMPK activation can promote proliferation and survival of LC cells via glycolysis induction. In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling. This is due to double-edged sword role of AMPK signaling in LC cells. Furthermore, AMPK signaling can regulate response of LC cells to chemotherapy and radiotherapy that are discussed in the current review.

Should all patients with hypertension be worried about developing severe coronavirus disease 2019 (COVID-19)?

BACKGROUND: Hypertension, the most common comorbidity among coronavirus disease 2019 (COVID-19) patients, is accompanied by worse clinical outcomes, but there is lack of evidence about prognostic factors among COVID-19 patients with hypertension. We have come up with some prognostic factors to predict the severity of COVID-19 among hypertensive patients. In addition, epidemiologic, clinical and laboratory differences among COVID-19 patients with and without underlying hypertension were evaluated. METHODS: Medical profiles of 598 COVID-19 cases were analyzed. Patients were divided into two comparative groups according to their positive or negative history of hypertension. Then, epidemiologic, clinical, laboratory and radiological features and also clinical outcomes were compared. RESULTS: 176 (29.4%) patients had underlying hypertension. Diabetes was significantly higher in hypertensive group [72 (40.9%) vs 76 (18%)] (P-value: 0.001). Cardiovascular and renal disorders were significantly higher in hypertensive patients. (P-value: 0.001 and 0.013 respectively). In COVID-19 patients with hypertension, severe/critical types were significantly higher. [42(23.8%) vs. 41(9.7%)], (P-value: 0.012). In the logistic regression model, Body mass index > 25 (ORAdj: 1.8, 95% CI: 1.2 to 2.42; P-value: 0.027), age over 60 (ORAdj: 1.26, 95% CI: 1.08 to 1.42; P-value: 0.021), increased hospitalization period (ORAdj: 2.1, 95% CI: 1.24 to 2.97; P-value: 0.013), type 2 diabetes (ORAdj: 2.22, 95% CI: 1.15 to 3.31; P-value: 0.001) and chronic kidney disease (ORAdj: 1.83, 95% CI: 1.19 to 2.21; P-value: 0.013) were related with progression of COVID-19. CONCLUSION: Hypertensive patients with Age > 60-year-old, BMI > 25 Kg/m2, CVD, diabetes and chronic kidney disease are associated with poor outcomes in those with COVID-19 infection.

The role of microRNA-338-3p in cancer: growth, invasion, chemoresistance, and mediators.

Cancer still remains as one of the leading causes of death worldwide. Metastasis and proliferation are abnormally increased in cancer cells that subsequently, mediate resistance of cancer cells to different therapies such as radio-, chemo- and immune-therapy. MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate expression of target genes at post-transcriptional level and capable of interaction with mRNA-coding genes. Vital biological mechanisms including apoptosis, migration and differentiation are modulated by these small molecules. MiRNAs are key players in regulating cancer proliferation and metastasis as well as cancer therapy response. MiRNAs can function as both tumor-suppressing and tumor-promoting factors. In the present review, regulatory impact of miRNA-338-3p on cancer growth and migration is discussed. This new emerging miRNA can regulate response of cancer cells to chemotherapy and radiotherapy. It seems that miRNA-338-3p has dual role in cancer chemotherapy, acting as tumor-promoting or tumor-suppressor factor. Experiments reveal anti-tumor activity of miRNA-338-3p in cancer. Hence, increasing miRNA-338-3p expression is of importance in effective cancer therapy. Long non-coding RNAs, circular RNAs and hypoxia are potential upstream mediators of miRNA-338-3p in cancer. Anti-tumor agents including baicalin and arbutin can promote expression of miRNA-338-3p in suppressing cancer progression. These topics are discussed to shed some light on function of miRNA-338-3p in cancer cells.

Lung cancer cells and their sensitivity/resistance to cisplatin chemotherapy: Role of microRNAs and upstream mediators.

Cisplatin (CP) is a well-known chemotherapeutic agent with excellent clinical effects. The anti-tumor activity of CP has been demonstrated in different cancers such as breast, cervical, reproductive, lung, brain, and prostate cancers. However, resistance of cancer cells to CP chemotherapy has led to its failure in eradication of cancer cells, and subsequent death of patients with cancer. Fortunately, much effort has been put to identify molecular pathways and mechanisms involved in CP resistance/sensitivity. It seems that microRNAs (miRs) are promising candidates in mediating CP resistance/sensitivity, since they participate in different biological aspects of cells such as proliferation, migration, angiogenesis, and differentiation. In this review, we focus on miRs and their regulation in CP chemotherapy of lung cancer, as the most malignant tumor worldwide. Oncogenic miRs trigger CP resistance in lung cancer cells via targeting various pathways such as Wnt/ß-catenin, Rab6, CASP2, PTEN, and Apaf-1. In contrast, onco-suppressor miRs inhibit oncogene pathways such as STAT3 to suppress CP resistance. These topics are discussed to determine the role of miRs in CP resistance/sensitivity. We also describe the upstream modulators of miRs such as lncRNAs, circRNAs, NF-κB, SOX2 and TRIM65 and their association with CP resistance/sensitivity in lung cancer cells. Finally, the effect of anti-tumor plant-derived natural compounds on miR expression during CP sensitivity of lung cancer cells is discussed.