An overview on mRNA-based vaccines to prevent monkeypox infection.

The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.

Fabrication of magnetic niosomal platform for delivery of resveratrol: potential anticancer activity against human pancreatic cancer Capan-1 cell.

Recently, the presence of different nanoparticles (NPs) has developed targeting drug delivery in treatment of cancer cell. Targeted drug delivery systems using NPs have shown great promise in improving the efficacy of intracellular uptake as well as local concentration of therapeutics with minimizing side effects. The current study planned to synthesized resveratrol-loaded magnetic niosomes nanoparticles (RSV-MNIONPs) and evaluate their cytotoxicity activity in pancreatic cancer cells. For this aim, magnetic nanoparticles (MNPs) were synthesized and loaded into niosomes (NIOs) by the thin film hydration technique and then characterized via DLS, FT-IR, TEM, SEM and VSM techniques. Moreover, the cytotoxic activity of the RSV-MNIONPs on the Capan-1 cells line was assessed by the MTT test. The distribution number of RSV-MNIONPs was gained about 80 nm and 95 nm with surface charge of - 14.0 mV by SEM and TEM analysis, respectively. RSV loading efficacy in NIOs was about 85%, and the drug releases pattern displayed a sustained discharge with a maximum amount about 35% and 40%, within 4 h in pH = 7.4 and pH = 5.8, respectively. The cytotoxicity of the RSV-MNIONPs in the presence of an external magnetic field is higher than that of the RSV, indicating enhanced cellular uptake in their encapsulated states. Furthermore, RSV loaded MNNPs were found to induce more cell cycle arrest at the G0/G1 checkpoint than free RSV. Compared with RSV-treated cells, the mRNA expression levels of BAX, Bcl2, FAS, P 53, Cyclin D and hTERT, were significantly changed in cells treated with RSV loaded MNNPs. The niosomes NPs approaches have been widely used to attain higher solubility, improved bioavailability, enhanced stability, and control delivery of RSV. Our formulation displayed antitumor activity and can be considered an appropriate carrier with a great potential for future usage in cancer therapy.

The role of specialized pro-resolving mediators (SPMs) in inflammatory arthritis: A therapeutic strategy.

Rheumatoid arthritis (RA) is classified as a persistent inflammatory autoimmune disorder leading to the subsequent erosion of articular cartilage and bone tissue originating from the synovium. The fundamental objective of therapeutic interventions in RA has been the suppression of inflammation. Nevertheless, conventional medicines that lack target specificity may exhibit unpredictable effects on cell metabolism. In recent times, there has been evidence suggesting that specialized pro-resolving mediators (SPMs), which are lipid metabolites, have a role in facilitating the resolution of inflammation and the reestablishment of tissue homeostasis. SPMs are synthesized by immune cells through the enzymatic conversion of omega-3 fatty acids. In the context of RA, there is a possibility of dysregulation in the production of these SPMs. In this review, we delve into the present comprehension of the endogenous functions of SPMs in RA as lipids that exhibit pro-resolutive, protective, and immunoresolvent properties.

An overview of the role of Niemann-pick C1 (NPC1) in viral infections and inhibition of viral infections through NPC1 inhibitor.

Viruses communicate with their hosts through interactions with proteins, lipids, and carbohydrate moieties on the plasma membrane (PM), often resulting in viral absorption via receptor-mediated endocytosis. Many viruses cannot multiply unless the host's cholesterol level remains steady. The large endo/lysosomal membrane protein (MP) Niemann-Pick C1 (NPC1), which is involved in cellular cholesterol transport, is a crucial intracellular receptor for viral infection. NPC1 is a ubiquitous housekeeping protein essential for the controlled cholesterol efflux from lysosomes. Its human absence results in Niemann-Pick type C disease, a deadly lysosomal storage disorder. NPC1 is a crucial viral receptor and an essential host component for filovirus entrance, infection, and pathogenesis. For filovirus entrance, NPC1's cellular function is unnecessary. Furthermore, blocking NPC1 limits the entry and replication of the African swine fever virus by disrupting cholesterol homeostasis. Cell entrance of quasi-enveloped variants of hepatitis A virus and hepatitis E virus has also been linked to NPC1. By controlling cholesterol levels, NPC1 is also necessary for the effective release of reovirus cores into the cytoplasm. Drugs that limit NPC1's activity are effective against several viruses, including SARS-CoV and Type I Feline Coronavirus (F-CoV). These findings reveal NPC1 as a potential therapeutic target for treating viral illnesses and demonstrate its significance for several viral infections. This article provides a synopsis of NPC1's function in viral infections and a review of NPC1 inhibitors that may be used to counteract viral infections. Video Abstract.

The effect of flaxseed supplementation on sex hormone profile in adults: a systematic review and meta-analysis.

Inconsistent data suggest that flaxseed supplementation may have a role in sex hormones. We aimed to carry out a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating effects of flaxseed supplementation on sex hormone profile. PubMed, Scopus, Embase, Cochrane Library, Web of Science databases, and Google Scholar were searched up to March 2023. Standardized mean difference (SMD) was pooled using a random-effects model. Sensitivity analysis, heterogeneity, and publication bias were reported using standard methods. The quality of each study was evaluated with the revised Cochrane risk-of-bias tool for randomized trials, known as RoB 2. Finding from ten RCTs revealed that flaxseed supplementation had no significant alteration in follicle-stimulating hormone (FSH) (SMD: -0.11; 95% CI: -0.87, 0.66: p = 0.783), sex hormone-binding globulin (SHBG) (SMD: 0.35; 95% CI: -0.02, 0.72; p = 0.063), total testosterone (TT) levels (SMD: 0.17; 95% CI: -0.07, 0.41; p = 0.165), free androgen index (FAI) (SMD = 0.11, 95% CI: -0.61, 0.83; p = 0.759), and dehydroepiandrosterone sulfate (DHEAS) (SMD: 0.08, 95%CI: -0.55, 0.72, p = 0.794). Flaxseed supplementation had no significant effect on sex hormones in adults. Nevertheless, due to the limited included trials, this topic is still open and needs further studies in future RCTs.

FOXO1, a tiny protein with intricate interactions: Promising therapeutic candidate in lung cancer.

Nowadays, lung cancer is the most common cause of cancer-related deaths in both men and women globally. Despite the development of extremely efficient targeted agents, lung cancer progression and drug resistance remain serious clinical issues. Increasing knowledge of the molecular mechanisms underlying progression and drug resistance will enable the development of novel therapeutic methods. It has been revealed that transcription factors (TF) dysregulation, which results in considerable expression modifications of genes, is a generally prevalent phenomenon regarding human malignancies. The forkhead box O1 (FOXO1), a member of the forkhead transcription factor family with crucial roles in cell fate decisions, is suggested to play a pivotal role as a tumor suppressor in a variety of malignancies, especially in lung cancer. FOXO1 is involved in diverse cellular processes and also has clinical significance consisting of cell cycle arrest, apoptosis, DNA repair, oxidative stress, cancer prevention, treatment, and chemo/radioresistance. Based on the critical role of FOXO1, this transcription factor appears to be an appropriate target for future drug discovery in lung cancers. This review focused on the signaling pathways, and molecular mechanisms involved in FOXO1 regulation in lung cancer. We also discuss pharmacological compounds that are currently being administered for lung cancer treatment by affecting FOXO1 and also point out the essential role of FOXO1 in drug resistance. Future preclinical research should assess combination drug strategies to stimulate FOXO1 and its upstream regulators as potential strategies to treat resistant or advanced lung cancers.

Targeting long noncoding RNAs in neuroblastoma: Progress and prospects.

Neuroblastoma (NB) is the third most prevalent tumor that mostly influences infants and young children. Although different treatments have been developed for the treatment of NB, high-risk patients have been reported to have low survival rates. Currently, long noncoding RNAs (lncRNAs) have shown an attractive potential in cancer research and a party of investigations have been performed to understand mechanisms underlying tumor development through lncRNA dysregulation. Researchers have just newly initiated to exhibit the involvement of lncRNAs in NB pathogenesis. In this review article, we tried to clarify the point we stand with respect to the involvement of lncRNAs in NB. Moreover, implications for the pathologic roles of lncRNAs in the development of NB have been discussed. It seems that some of these lncRNAs have promising potential to be applied as biomarkers for NB prognosis and treatment.

Role of m6A modification in dysregulation of Wnt/ß-catenin pathway in cancer.

N6-methyladenosine (m6A) modification is the most abundant post-transcriptional regulation of RNAs in eukaryotes. Dysregulation of m6A readers, writers, and erasers can significantly promote tumorigenesis by altering the expression of various genes. Wnt/ß-catenin is an evolutionarily conserved signaling pathway that has recently been linked to the pathogenesis of many cancers. Given the significance of this pathway in regulating normal tissue homeostasis and stem cell differentiation, a subtle understanding of the molecular mechanism underlying its dysregulation is required for effective targeting. There is mounting evidence that m6A regulators are highly implicated in the dysregulation of the Wnt/ß-catenin signaling pathway. Since m6A regulators can affect Wnt pathway components and dysregulation of either leads to carcinogenesis, this study aims to clarify the relationship between m6A regulators and the Wnt/ß-catenin signaling pathway to investigate their combined impact on tumorigenesis.

MicroRNA-155 acts as a potential prognostic and diagnostic factor in patients with ankylosing spondylitis by modulating SOCS3.

BACKGROUND: Ankylosing spondylitis (AS) is a progressive inflammatory disease. Our primary objective was to explore the role of miR-155 and its targeted factors in AS pathogenesis. METHODS AND RESULTS: PBMCs were isolated from 30 AS patients and 30 healthy individuals using the Ficoll-hypaque isolation approach. The expression of miR-155 and its associated targets, including Suppressor Of Cytokine Signaling 3 (SOCS3), STAT3, and IL-21, were determined using qT-qPCR. Then, PBMCs were cultured, and the effect of miR-155, SOCS3 siRNA (to suppress its expression), pEFSOCS3 (enforced expression), and their combination were investigated by qRT-PCR and western blotting. We also treated the cultured PBMCs with Brefeldin A, a potent inhibitor of cytokine secretion, to determine its effect on IL-21 expression and secretion. In addition, the association between miR-155 and patients' clinicopathological features was examined. The results showed that miR-155, IL-21, and STAT3 were increased in patients with AS, while SOCS3 had decreasing expression trend. It was also determined that miR-155 alleviates SOCS3 expression and increases IL-21 and STAT3 expression; it had a prominent effect when combined with SOCS3 siRNA. Besides, we showed that simultaneous transfection of miR-155 and pEFSOCS3 had no significant effect on IL-21 and STAT3 expression, revealing that miR-155 could alleviate the enforced expression of SOCS3. It was also proven that Brefledine A led to IL-21 up-regulation or accumulation while relieving its secretion. Also, a significant correlation between miR-155 and pathological features of AS patients was found. CONCLUSION: miR-155 acts as a potential prognostic and diagnostic biomarker. Its up-regulation leads to the down-regulation of SOCS3 and increased expression of IL-21 and STAT3 as characteristic of TH-17 lymphocytes, leading to worsening inflammatory conditions in patients with AS.

A giant ureteral stone in a 32-year-old man: a case report.

Giant ureteral calculi are defined as stones greater than 5 cm in length or circumference. These giant calculi can cause blockage of the ureter, dilation of the kidney and also decreased kidney function if not treated in time. The patient in this report presented with complaints of bilateral episodic pain of the bilateral lumbar region. Kidney, ureter and bladder (KUB) X-ray test showed a large bilateral ureteral stone about 14 cm in length and 106 g weight in the left ureter and 3 cm longitudinal diameter in the right ureter and also a staghorn stone in the left upper collecting system. Thereafter, the ureteric calculi were managed successfully using the combination of open and endoscopic techniques.

Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

PURPOSE: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. MATERIALS AND METHODS: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. RESULTS: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. CONCLUSIONS: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.

Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

ABSTRACT Purpose: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. Materials and Methods: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. Results: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. Conclusions: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.

Antioxidant Effects of Brown Algae Sargassum on Sperm Parameters: CONSORT-Compliant Article.

The occurrence of oxidative stress during the sperm freeze-thaw cycles affects the sperm parameters and eventually leads to a decrease in its reproductive potential. Sperm protection against oxidative reactions during freezing is done by antioxidants. Since the selection of a suitable sperm cryopreservation bank is effective in maintaining acceptable reproductive potential and motility of sperm during cryopreservation.This study aimed to evaluate the antioxidant effects of different doses of the extract of brown algae Sargassum on oxidative stress and frozen human sperm parameters.We conducted a randomized controlled trial on the semen samples from 11 healthy men in the age group of 25 to 36 years. The samples were collected by masturbation after 3 to 5 days of abstinence from ejaculation. The specimens were divided into 3 equal parts, including 1 control group and 2 experimental groups.The 2 experimental groups were frozen using the rapid solidification technique with Sargassum extract at doses of 250 and 500 µg/mL.Motility and morphology of sperms were measured using a computer system and CASA software and the amount of reactive oxygen species was determined using Oxisperm kit.Sargassum extract significantly decreased the amount of reactive oxygen species (P < 0.005) and at doses of 250 and 500 µg/mL, significantly increased the overall motility (P < 0.006) and progressive motility (P < 0.007) after solidification, but did not affect the normal morphology of sperms.The addition of ethanol extract of Sargassum prevents reactive oxygen species production during the solidification process and improves sperm motility at doses of 250 and 500 µg/mL.

Which patients are at higher risk for residual valves after posterior urethral valve ablation?

PURPOSE: To find patients at high risk of obstructive remnant leaflets after valve ablation among boys with posterior urethral valve (PUV), we evaluated any possible relationship between preoperative findings in our patients and residual obstructive leaflets after valve ablation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 55 patients with PUV that was treated by the same surgeon between 2008 and 2012. Of these, 37 patients (67.3%) had no obstructive remnant leaflets (group A) and 18 patients (32.7%) had obstructive remnant leaflets (group B) in follow-up cystoscopy. Preoperative clinical and radiological findings were evaluated and compared between the groups. RESULTS: AMONG ALL THE PREOPERATIVE DATA WE EXAMINED, THE ANALYSIS REVEALED THAT AGE AT THE TIME OF SURGERY (MEDIAN AGE: group A, 15 months; group B, 7 months; p=0.017), echogenicity of kidneys (p<0.05), presence of vesicoureteral reflux (p<0.05), and grade of reflux (p<0.05) were significantly different between the groups. Method of valve ablation, anterior-posterior diameters of the renal pelvis, renal cortical thickness, bladder wall thickening, and scarring on the dimercaptosuccinic acid scan showed no significant differences between the two groups. CONCLUSIONS: In our patients, younger age at surgery time, hyperechogenicity of renal parenchyma, presence of vesicoureteral reflux, and grade 4 or 5 reflux before surgery had a significant relationship with residual valves. More studies may result in enhanced management of patients at high risk of residual valves after PUV ablation, because the sooner the obstruction is resolved entirely, the better the outcome.

Result of endoureterotomy in the management of primary obstructive megaureter in the first year of life: preliminary report.

PURPOSE: The present study aimed to investigate the efficacy of endoureterotomy in patients who were less than 1-year-old with primary obstructive megaureter (POMU). PATIENTS AND METHODS: Three of 10 patients with POMU aged between 2 and 12 months for whom conservative management was not applicable had recurrent urinary tract infection (UTI) and urosepsis, while the rest had decreased renal function. After obtaining the clinical history and performing physical examinations and imaging studies (ultrasonography, voiding cystourethrography (VCUG), radionuclide renal scan), the patients underwent endoureterotomy using a neonatal ureteroscope (4.5F) and Bugbee electrode with pure cutting current at the 6 o'clock position. A Double-J stent was inserted and removed 1 week later. This was followed by serial physical examination, renal function test, urine analysis, urine culture, and imaging studies in the 1st month and every 3 months after Double-J stent removal. RESULTS: Hydroureteronephrosis was significantly decreased in nine patients. Postoperative VCUG revealed no sign of iatrogenic vesicoureteral reflux. In addition, a follow-up renal scan showed remarkable improvement in the renal function in the patients who had decreased renal function, except for one patient in whom uncontrolled urosepsis developed in the follow-up; the patient underwent cutaneous ureterostomy. No UTI was detected in the group who presented with recurrent UTI and urosepsis. CONCLUSION: According to the results of our study, endoureterotomy may be an alternative in management of POMU. Of course, further studies with longer follow-up periods are needed to confirm the applicability of this method in patients younger than 1 year.