Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review.

Ovarian cancer is among the most lethal gynecological cancers, primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy. Drug resistance (DR) poses the most significant challenge in treating patients with existing drugs. The Food and Drug Administration (FDA) has recently approved three new therapeutic drugs, including two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and niraparib) and one vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) for maintenance therapy. However, resistance to these new drugs has emerged. Therefore, understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management. In this review, we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

The Impact of Pulmonary Hydatid Cyst Rupture on COVID-19 Symptom Severity.

BACKGROUND: Co-infection with other microorganisms such as parasites in patients with COVID-19 can affect the clinical outcome and require prompt diagnosis and appropriate therapy. CASE PRESENTATION: We present a case of an adult male with chest pain, dyspnea, cough, diplopia, and anorexia who was confirmed to have acute COVID-19 pneumonia. 2 weeks prior to admission, a hydatid lung cyst was identified on examination, but the patient refused surgery. Thoracoabdominal computed tomography (CT) revealed a rupture of the lung hydatid cyst and co-infection with COVID-19. The patient has prescribed a treatment protocol for COVID-19 and albendazole. Despite measures taken to manage severe inflammation and decreasing blood oxygen levels, the patient required admission to the intensive care unit (ICU) and intubation. After approximately 3 weeks of hospitalization, the patient was successfully extubated and discharged uneventfully from the hospital. Oral albendazole was prescribed for follow-up treatment. CONCLUSION: Our case highlights the importance of considering hydatid cysts in the differential diagnosis of patients with COVID-19, especially those living in endemic areas.

Aminoglycosides: single- or multiple-daily dosing? An updated qualitative systematic review of randomized trials on toxicity and efficacy.

INTRODUCTION: Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides. OBJECTIVE: In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs). METHODS: We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords "aminoglycosides", "pharmacokinetics", "ODD", "MDD", "once daily", "multiple daily", "dosing regimen", "nephrotoxicity", "ototoxicity", "efficacy", "safety", and "toxicity". As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD versus MDD of aminoglycosides. A total number of 21 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years. RESULTS: The most common clinical condition in the included studies was cystic fibrosis. CONCLUSION: In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.

Circulating tumor cells and circulating tumor DNA in breast cancer diagnosis and monitoring.

Liquid biopsy, including both circulating tumor cells and circulating tumor DNA, is becoming more popular as a diagnostic tool in the clinical management of breast cancer. Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance. Thus, these circulating markers serve as tools for cancer assessing and monitoring through a simple, non-invasive blood draw. However, despite several study results currently noting a potential clinical impact of ctDNA mutation tracking, the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it. This review focuses on understanding circulating tumor biomarkers, especially in breast cancer.

Differences in clinical and lab characteristics of sepsis between opium user patients and patients with no illicit drug addiction.

BACKGROUND: Sepsis is a significant cause of mortality worldwide. This study aimed to compare clinical and laboratory characteristics of sepsis in patients addicted to illicit drugs versus patients with no illicit drug addiction. METHODS: In this cross-sectional study, all patients hospitalized with sepsis diagnosis were recruited within six months from September to March 2019. Sixty patients for each group (illicit drug-addicted and non-addicted individuals) were selected. The data relating to illicit drug consumption, serum indices, the current focus of infection, duration of hospitalization, and disease outcomes were collected. Patients who had an illicit drug addiction were compared with non-addicted patients in terms of clinical and laboratory parameters. The data collected were analyzed using SPSS software (version 19). RESULTS: The bacterial load in the urine culture was statistically significant in both groups and higher in the non-addicted group. The frequency distributions of focus of infection, duration of hospitalization, and outcome were not significantly different between the two groups. The serum sodium and total neutrophils were significantly higher in the addicted group. However, the MCHC level was significantly lower (p<0.05). CONCLUSION: Opium may have stimulated the immune system and reduced bacterial infection in septic patient users.

Compliance with Antibiotics Prophylaxis Guideline in Surgical Patients in ICUs of a Teaching Referral Hospital.

Antimicrobial prophylaxis used for surgical procedures remains one of the measures for the prevention of surgical site infections (SSIs). The present study was designed to assess the compliance with clinical practice guideline for antimicrobial prophylaxis in variable surgeries conducted in the intensive care units (ICUs) of a major referral hospital. This cross-sectional investigation was carried out by prospective data collected from October 2017 to March 2018 in the intensive care unit (ICU) of Nemazi hospital in Shiraz. Demographic characteristics, surgery type as well as antibiotic treatment were gathered from medical records and entered in data collection forms. We reviewed compliance and adherence of prophylactic antibiotic administration to the Infectious Diseases Society of America (IDSA) guideline and evaluated the courses of antimicrobial drugs. If an antibiotic administrated for surgical prophylaxis was different from the guideline, the antibiotic was classified as non-guideline-based antibiotics. Most patients participated in this study were male (64.5%). Only 8.75% of the administrated antibiotics chosen for surgical prophylaxis were found to be appropriate antibiotic prescriptions; however, those patients receiving appropriate antibiotics prescribed an inappropriate dosage. In addition, the antibiotics were administrated with inappropriate durations in all cases. Our findings indicated that adherence to the IDSA international guideline seems to be far from ideal in Namazi hospital for antimicrobial prophylaxis, resulting in the unsuitable administration of a wide variety of antibiotics.

MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient's quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

The effect of polyunsaturated fatty acids on the severity and mortality of COVID patients: A systematic review.

BACKGROUND: Covid-19 mortality is largely associated with a severe increase in inflammatory cytokines and polyunsaturated fatty acids (PUFAs) play an important role in modulating immune pathways and inflammatory responses; so this study was done to evaluate the effect of polyunsaturated fatty acids on the prognosis of Covid-19 disease. METHODS AND MATERIALS: A comprehensive search was conducted in PubMed, Scopus and Web of Science. For systematic identification, the search was performed based on the following keywords COVID-19, SARS-CoV-2, COVID, Coronavirus Disease 19, SARS COV- 2 Infection, SARS-CoV-2, COVID19, Coronavirus Disease, Fatty Acids, Omega-3, Omega-3 Fatty Acid, Omega-6, n 3 Fatty and Omega-9 in the mentioned databases, using OR, and AND. All searched articles were included in the study and retrieved, and End-Note X7 software was used to manage the studies. RESULTS: Findings on the relationship between omega-3 and omega-6 fatty acids and the risk of Covid-19 are various, but omega-3 supplements have been found to be 12 to 21% effective in reducing the risk of Covid-19. Most studies emphasized the increasing severity of the disease and the need for mechanical ventilation and hospitalization due to polyunsaturated fatty acid deficiency. It is also demonstrated that omega-3 fatty acid deficiency increased mortality in patients with Covid-19. However, there is also a warning that in critical cases, elevated levels of fatty acids in patients' lungs and a cytokine storm are the main reasons for mortality in Covid-19 patients. CONCLUSION: Polyunsaturated fatty acids can reduce the risk of covid-19 which could be considered as a preventative, inexpensive and safe method. However, the risk of taking high-dose omega-3 supplements before or during SARS-COV-2 infection needs to be investigated.

Topical treatment of cutaneous leishmaniasis lesions using quercetin/ Artemisia-capped silver nanoparticles ointment: Modulation of inflammatory response.

Leishmaniasis is a major health issue that affects people all over the world, producing considerable morbidity and mortality in Asia, Africa, and the Americas, and existing treatments have significant side effects. Nowadays, the development of nanoscale materials such as biogenic silver nanoparticles has attracted much medical attraction. In this study, AgNPs were synthesized from leaf extract of Artemisia aucheri. Biosynthesized AgNPs were analyzed by UV-visible spectroscopy, dynamic light scattering and zeta potential, fourier transform infrared spectroscopy and field emission scanning electron microscopy. Biosynthesized AgNPs were examined for anti-leishmanial and antibacterial activity. The in vivo study was conducted by treating the L. major infected BALB/c mice with quercetin/ artemisia-capped silver nanoparticles ointment topically for 21 consecutive days. The in vitro and in vivo results showed that the ointment containig quercetin/artemisia-capped silver nanoparticles have the potential to decrease inflammatory responses and enhance wound healing with granulation tissue formation compared to the untreated group. Therefore, biogenic nanoparticles are safe, eco-friendly, and easy to synthesize and could be considered as an alternative regimen for treatment of L. major.

Effectiveness of the adipose stem cells in burn wound healing: literature review.

Adipose- stem cells (ASCs) have received much attention in the recent years and several articles have investigated the role of these cells on burn wound healing. To understand the outcomes of the ASCs therapy on burn wound healing, a systematic review was performed. This study was conducted by searching in Pubmed, ISI, and Scopus until May 2021. Thirty-six animal studies were included in this study. The findings revealed that although treatment with ASCs somewhat enhanced the healing rate, cultured ASCs on scaffolds or its combination with hydrogels could significantly increase the viability of ASCs and promote rate of healing. However, clinical studies are necessary to gain a better understanding of the role of ASCs in burn wound healing.

The effect of low serum calcium level on the severity and mortality of Covid patients: A systematic review and meta-analysis.

INTRODUCTION: Imbalances of various electrolytes, including calcium, are associated with the prognosis of Covid disease. This study investigated the relationship between serum calcium and clinical outcomes in patients with COVID-19. METHOD: This study is a systematic review and meta-analysis by searching PubMed, Scopus, web of sciences until August 2021 using the keywords COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID, coronavirus disease, SARS-COV-infection. 2, SARS-COV-2, COVID19, calcium, calcium isotopes, calcium radioisotopes, hypercalcemia, and hypocalcemia were performed. Heterogeneity of studies was investigated using I2 index, data were analyzed using meta-analysis (random effects model) with Comprehensive Meta-Analysis Software software. RESULTS: Finally, 25 articles were included in the study. Clinical data from 12 articles showed that 59% (95% confidence interval [CI]: 0.49-0.68) of people with COVID-19 have hypocalcemia. The results of meta-analysis showed that hypocalcemia was significantly associated with severity of the disease (p = .002), mortality in patients with COVID-19 (odds ratio [OR] = 6.99, 95% CI: 2.71-17.99), number of hospitalization days (p < .001) and admission to the intensive care unit (OR = 5.09, 95% CI: 2.14-12.10). The results also showed that there is a direct relationship between low serum calcium levels with increasing D-dimer levels (p = .02) and decreasing lymphocyte counts (p = .007). CONCLUSION: Based on the results of meta-analysis in people with lower calcium, mortality and complications are higher, therefore, serum calcium is a prognostic factor in determining the severity of the disease. Consequently, it is suggested that serum calcium levels should be considered in initial assessments.

Enhanced anti-tumor efficacy and reduced cardiotoxicity of doxorubicin delivered in a novel plant virus nanoparticle.

Plant viruses are one of the newly applied nanoparticles as drug delivery vehicles. Here, we investigated drug delivery performance of Johnson grass chlorotic stripe mosaic virus (JgCSMV) conjugated to folic acid (FA) for targeted delivery of doxorubicin (Dox). The FA-JgCSMV-Dox complex was synthesized and characterized using spectrophotometry, native and denaturing gel electrophoresis and transmission electron microscopy, which disclosed that JgCSMV virions encapsulated Dox and showed comparable size and morphology to the native particles. The JgCSMV nanoparticles loaded with Dox showed a sustained drug release profile in tumor tissue and improved the uptake of Dox in breast cancer cells, leading to enhanced tumor homing. Lastly, we demonstrated that FA-JgCSMV-Dox reduced the tumor growth and cardiotoxicity of athymic mice bearing human breast cancer xenografts in comparison to free Dox. This study is the first report on applicability of JgCSMV for Dox delivery with superior benefits over generally marketed formulations of doxorubicin.

Plant virus nanoparticles: Novel and robust nanocarriers for drug delivery and imaging.

Nanoparticles have been gained much attention for biomedical applications. A promising type of nanocarriers is viral nanoparticles (VNPs) which are natural bio-nanomaterials derived from different type of viruses. Amongst VNPs, plant VNPs present several pros over general nanoparticles such as liposomes, dendrimers or quantum dots. Some of these advantages include: degradability, safety for human, known structures to atomic level, possibility of attaching ligand with vigorous control on structure, availability for genetic and chemical manipulations and very flexible methods to prepare them. Variety of plant viruses have been modified by chemical and genetic modification of their inner cavities and their outer-surfaces. These modifications provide suitable sites for attachment of markers and drug molecules for vascular imaging and tumor targeting. In this review a brief description of plant virus nanoparticles and their biomedical applications especially in drug delivery is provided. The methods of loading cargos in these VNPs and their final biofate are also reviewed.