CRISPR-Driven Biosensors: A New Frontier in Rapid and Accurate Disease Detection.

This comprehensive review delves into the advancements and challenges in biosensing, with a strong emphasis on the transformative potential of CRISPR technology for early and rapid detection of infectious diseases. It underscores the versatility of CRISPR/Cas systems, highlighting their ability to detect both nucleic acids and non-nucleic acid targets, and their seamless integration with isothermal amplification techniques. The review provides a thorough examination of the latest developments in CRISPR-based biosensors, detailing the unique properties of CRISPR systems, such as their high specificity and programmability, which make them particularly effective for detecting disease-associated nucleic acids. While the review focuses on nucleic acid detection due to its critical role in diagnosing infectious diseases, it also explores the broader applications of CRISPR technology in detecting non-nucleic acid targets, thereby acknowledging the technology's broader potential. Additionally, the review identifies existing challenges, such as the need for improved signal amplification and real-world applicability, and offers future perspectives aimed at overcoming these hurdles. The ultimate goal is to advance the development of highly sensitive and specific CRISPR-based biosensors that can be used widely for improving human health, particularly in point-of-care settings and resource-limited environments.

Microfluidic systems for modeling digestive cancer: a review of recent progress.

Purpose. This review aims to highlight current improvements in microfluidic devices designed for digestive cancer simulation. The review emphasizes the use of multicellular 3D tissue engineering models to understand the complicated biology of the tumor microenvironment (TME) and cancer progression. The purpose is to develop oncology research and improve digestive cancer patients' lives.Methods. This review analyzes recent research on microfluidic devices for mimicking digestive cancer. It uses tissue-engineered microfluidic devices, notably organs on a chip (OOC), to simulate human organ function in the lab. Cell cultivation on modern three-dimensional hydrogel platforms allows precise geometry, biological components, and physiological qualities. The review analyzes novel methodologies, key findings, and technical progress to explain this field's advances.Results. This study discusses current advances in microfluidic devices for mimicking digestive cancer. Micro physiological systems with multicellular 3D tissue engineering models are emphasized. These systems capture complex biochemical gradients, niche variables, and dynamic cell-cell interactions in the tumor microenvironment (TME). These models reveal stomach cancer biology and progression by duplicating the TME. Recent discoveries and technology advances have improved our understanding of gut cancer biology, as shown in the review.Conclusion. Microfluidic systems play a crucial role in modeling digestive cancer and furthering oncology research. These platforms could transform drug development and treatment by revealing the complex biology of the tumor microenvironment and cancer progression. The review provides a complete summary of recent advances and suggests future research for field professionals. The review's major goal is to further medical research and improve digestive cancer patients' lives.

Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches.

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful.

Association between cytomegalovirus infection and neurological disorders: A systematic review.

Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.

Understanding the Role of Galectin-1 in Heart Failure: A Comprehensive Narrative Review.

Heart failure (HF) is the fastest-growing cardiovascular condition worldwide. The immune system may play a role in the development of HF since this condition is associated with elevated pro-inflammatory cytokine levels. HF is a life-threatening disease, and there is an increasing demand for diagnostic biomarkers, prognostic factors, and therapeutic agents that can help treat it. Galectin-1 (Gal-1) is the prototype galectin of the lectin family. Multiple signal transduction pathways are regulated by Ras proteins, which act as a molecular switch in cells. Gal-1 regulates T and B cell activation, differentiation, and survival. Gal-1 has been linked to inflammation. Activated T cells produce Gal-1 through an autocrine apoptotic mechanism involving MEK1/ERK and p38 MAPK. In the cardiovascular system, atherosclerosis is facilitated by Gal-1. Heart disease, myocardial infarction, hypertension, and stroke can be caused by atherosclerotic plaque. HF and heart hypertrophy are caused by decreased cardiac L-type Ca2+ channel activity. Deregulation of Gal-1 and CaV1.2 in pathological cardiac hypertrophy suggests a possible target for anti-hypertrophic therapy. Rat hypertrophic cardiomyocytes express Gal-1 and CaV1.2 channels simultaneously. It has been reported that diastolic dysfunction (DD) is associated with elevated Gal-1 levels. The high Gal-1 level in subjects led to the lowest cumulative survival as a composite endpoint. Incidences of HF, DD, and serum Gal-1 levels correlated significantly. The ejection fraction was negatively correlated with Gal-1 and CRP concentrations. Based on two different approaches in mice and humans, Gal-1 was identified as a potential mediator of HF.

Computational design of a multi-epitope vaccine candidate against Langya henipavirus using surface proteins.

In July 2022, Langya henipavirus (LayV) was identified in febrile patients in China. There is currently no approved vaccine against this virus. Therefore, this research aimed to design a multi-epitope vaccine against LayV using reverse vaccinology. The best epitopes were selected from LayV's fusion protein (F) and glycoprotein (G), and a multi-epitope vaccine was designed using these epitopes, adjuvant, and appropriate linkers. The physicochemical properties, antigenicity, allergenicity, toxicity, and solubility of the vaccine were evaluated. The vaccine's secondary and 3D structures were predicted, and molecular docking and molecular dynamics (MD) simulations were used to assess the vaccine's interaction and stability with toll-like receptor 4 (TLR4). Immune simulation, codon optimization, and in silico cloning of the vaccine were also performed. The vaccine candidate showed good physicochemical properties, as well as being antigenic, non-allergenic, and non-toxic, with acceptable solubility. Molecular docking and MD simulation revealed that the vaccine and TLR4 have stable interactions. Furthermore, immunological simulation of the vaccine indicated its ability to elicit immune responses against LayV. The vaccine's increased expression was also ensured using codon optimization. This study's findings were encouraging, but in vitro and in vivo tests are needed to confirm the vaccine's protective effect.Communicated by Ramaswamy H. Sarma.

PCL-based nanoparticles for doxorubicin-ezetimibe co-delivery: A combination therapy for prostate cancer using a drug repurposing strategy.

Introduction: Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment. Methods: In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures. Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells. Conclusion: Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.

A Novel Vision of Reinforcing Nanofibrous Masks with Metal Nanoparticles: Antiviral Mechanisms Investigation.

Prevention of spreading viral respiratory disease, especially in case of a pandemic such as coronavirus disease of 2019 (COVID-19), has been proved impossible without considering obligatory face mask-wearing protocols for both healthy and contaminated populations. The widespread application of face masks for long hours and almost everywhere increases the risks of bacterial growth in the warm and humid environment inside the mask. On the other hand, in the absence of antiviral agents on the surface of the mask, the virus may have a chance to stay alive and be carried to different places or even put the wearers at risk of contamination when touching or disposing the masks. In this article, the antiviral activity and mechanism of action of some of the potent metal and metal oxide nanoparticles in the role of promising virucidal agents have been reviewed, and incorporation of them in an electrospun nanofibrous structure has been considered an applicable method for the fabrication of innovative respiratory protecting materials with upgraded safety levels.

In silico design and immunoinformatics analysis of a universal multi-epitope vaccine against monkeypox virus.

Monkeypox virus (MPXV) outbreaks have been reported in various countries worldwide; however, there is no specific vaccine against MPXV. In this study, therefore, we employed computational approaches to design a multi-epitope vaccine against MPXV. Initially, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), linear B lymphocytes (LBL) epitopes were predicted from the cell surface-binding protein and envelope protein A28 homolog, both of which play essential roles in MPXV pathogenesis. All of the predicted epitopes were evaluated using key parameters. A total of 7 CTL, 4 HTL, and 5 LBL epitopes were chosen and combined with appropriate linkers and adjuvant to construct a multi-epitope vaccine. The CTL and HTL epitopes of the vaccine construct cover 95.57% of the worldwide population. The designed vaccine construct was found to be highly antigenic, non-allergenic, soluble, and to have acceptable physicochemical properties. The 3D structure of the vaccine and its potential interaction with Toll-Like receptor-4 (TLR4) were predicted. Molecular dynamics (MD) simulation confirmed the vaccine's high stability in complex with TLR4. Finally, codon adaptation and in silico cloning confirmed the high expression rate of the vaccine constructs in strain K12 of Escherichia coli (E. coli). These findings are very encouraging; however, in vitro and animal studies are needed to ensure the potency and safety of this vaccine candidate.

Comparison of Efficacy and Safety of Levetiracetam Versus Phenytoin for Post-craniotomy Seizure Prophylaxis.

Background: Superiority of levetiracetam over phenytoin for postcraniotomy seizure prophylaxis in patients with a supratentorial brain tumor is controversial. We aimed to evaluate the efficacy of levetiracetam versus phenytoin for postcraniotomy seizure prophylaxis in supratentorial brain tumor. Methods: In a randomized controlled trial study, 80 patients with a supratentorial brain tumor who underwent craniotomy were allocated to levetiracetam or phenytoin group, 40 patients each. Seizure prophylaxis was started 5 days before the surgery and continued until 90 days after surgery. Phenytoin group received 100 mg oral phenytoin 3 times a day. The levetiracetam group received 500 mg oral levetiracetam 2 times a day. The primary outcome was the incidence of postcraniotomy seizures. The secondary outcome measure was the safety profile of the drugs. Results: All patients of the phenytoin group and 39 patients of levetiracetam completed the study. Two seizures developed in the study population, 1 in the phenytoin group (2.5%) and 1 in the levetiracetam group (2.6%) (P = 0.710). Renal or hepatic dysfunction was not observed in any patients. Wound hematoma was seen in 5 patients (12.5%) of the phenytoin and 6 patients (15.4%) of the levetiracetam group (P = 0.481). Skin rash developed in 3 patients (7.5%) of the phenytoin group and no patient of the levetiracetam group (P = 0.132). Thrombocytopenia was detected in 1 patient of the phenytoin group (2.5%) and no patient of the levetiracetam group (P = 0.511). None of the adverse events led to drug withdrawal. Conclusion: These results reveal no superiority of levetiracetam over phenytoin for postcraniotomy seizure prophylaxis in supratentorial brain tumor.

Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12.

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics for the treatment of COVID-19 patients with cytokine storm. The interaction of MTZ with key cytokines was investigated using molecular docking studies. MTZ-analogues, and its structurally similar FDA-approved drugs were also virtually screened against interleukin-12 (IL-12). Moreover, their mechanism of inhibition regarding IL-12 binding to IL-12 receptor was investigated by measuring the change in volume and area. IL-12-metronidazole complex is found to be more stable than all other cytokines under study. Our study also revealed that the active sites of IL-12 are inhibited from binding to its target, IL-12 receptor, by modifying the position of the methyl and hydroxyl functional groups in MTZ. Three MTZ analogues, metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5-nitroimidazol-2-yl]-N-methylmethanimine-oxide, and two FDA-approved drugs acyclovir (ACV), and tetrahydrobiopterin (THB) were also found to prevent binding of IL-12 to IL-12 receptor similar to MTZ by changing the surface and volume of IL-12 upon IL-12-drug/ligand complex formation. According to the RMSD results, after 100 ns MD simulations of human IL-12-MTZ/ACV/THB drug complexes, it was also observed that each complex was swinging within a few Å compared to their corresponding docking poses, indicating that the docking poses were reliable. The current study demonstrates that three FDA-approved drugs, namely, metronidazole, acyclovir and tetrahydrobiopterin, are potential repurposable treatment options for overexpressed serum cytokines found in COVID-19 patients. Similar approach is also useful to develop therapeutics against other human disorders.Communicated by Ramaswamy H. Sarma.

The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study.

BACKGROUND: Despite the improvements to enhance skin flap viability, the effects of ischemia-reperfusion (IR), oxidative stress, necrosis, and apoptosis are still challenging. Crocus sativus L. (Saffron) is highly noticeable due to its tissue-protective and antioxidant properties. So, we aimed to investigate its effects on skin flap viability, oxidative stress, apoptosis markers, histopathological changes, and mTOR/p-mTOR expression. MATERIALS AND METHODS: 40 Sprauge-Dawley rats, weighting 200-240 g, were divided into four groups including: (1) Sham (8 × 3 cm skin cut, without elevation); (2) Flap Surgery (8 × 3 cm skin flap with elevation from its bed); (3) Saffron 40 mg/kg + Flap Surgery; and (4) Saffron 80 mg/kg + Flap Surgery. Saffron was administrated orally for 7 days. At day 7, flap necrosis percentage, histopathological changes, malondialdehyde level, Myeloperoxidase and superoxide dismutase activity, Bax, Bcl-2, mTOR, and p-mTOR expression were measured. Protein expressions were controlled by ß-Actin. RESULTS: Saffron administration decreased flap necrosis percentage (p < 0.01), which was not dose-dependent. Treatment groups showed significant histological healing signs (Neovascularization, Fibroblast migration, Epithelialization, and Epithelialization thickness), decreased MDA content (p < 0.01), increased SOD (p < 0.01) and decreased MPO activity (p < 0.01). Bax and Bcl-2 expression, decreased and increased respectively in treated groups (p < 0.0001). mTOR and p-mTOR expression were not changed significantly in Saffron treated groups. CONCLUSION: Saffron could increase skin flap viability, alleviate necrosis, decrease oxidative stress and decrease apoptotic cell death, after skin flap surgery, but it acts independent of the mTOR pathway. So, Saffron could potentially be used clinically to enhance skin flap viability. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. https://www.springer.com/00266.

In silico design of a multi-epitope vaccine against HPV16/18.

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. RESULTS: In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. CONCLUSIONS: According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.

Role of Polyphenols on Gut Microbiota and the Ubiquitin-Proteasome System in Neurodegenerative Diseases.

Today, neurodegenerative diseases have become a remarkable public health challenge due to their direct relation with aging. Accordingly, understanding the molecular and cellular mechanisms occurring in the pathogenesis of them is essential. Both protein aggregations as a result of the ubiquitin-proteasome system (UPS) inefficiency and gut microbiota alternation are the main pathogenic hallmarks. Polyphenols upregulating this system may decrease the developing rate of neurodegenerative diseases. Most of the dietary intake of polyphenols is converted into other microbial metabolites, which have completely different biological properties from the original polyphenols and should be thoroughly investigated. Herein, several prevalent neurodegenerative diseases are pinpointed to explain the role of gut microbiota alternations and the role of molecular changes, especially UPS down-regulation in their pathogenesis. Some of the most important polyphenols found in our diet are explained along with their microbial metabolites in the body.

Ubiquitin-proteasome system and the role of its inhibitors in cancer therapy.

Despite all the other cells that have the potential to prevent cancer development and metastasis through tumour suppressor proteins, cancer cells can upregulate the ubiquitin-proteasome system (UPS) by which they can degrade tumour suppressor proteins and avoid apoptosis. This system plays an extensive role in cell regulation organized in two steps. Each step has an important role in controlling cancer. This demonstrates the importance of understanding UPS inhibitors and improving these inhibitors to foster a new hope in cancer therapy. UPS inhibitors, as less invasive chemotherapy drugs, are increasingly used to alleviate symptoms of various cancers in malignant states. Despite their success in reducing the development of cancer with the lowest side effects, thus far, an appropriate inhibitor that can effectively inactivate this system with the least drug resistance has not yet been fully investigated. A fundamental understanding of the system is necessary to fully elucidate its role in causing/controlling cancer. In this review, we first comprehensively investigate this system, and then each step containing ubiquitination and protein degradation as well as their inhibitors are discussed. Ultimately, its advantages and disadvantages and some perspectives for improving the efficiency of these inhibitors are discussed.

Multifunctional hydrogels for wound healing: Special focus on biomacromolecular based hydrogels.

Hydrogels are widely used for wound healing applications due to their similarity to the native extracellular matrix (ECM) and ability to provide a moist environment. However, lack of multifunctionality and low mechanical properties of previously developed hydrogels may limit their ability to support skin tissue regeneration. Incorporating various biomaterials and nanostructures into the hydrogels is an emerging approach to develop multifunctional hydrogels with new functions that are beneficial for wound healing. These multifunctional hydrogels can be fabricated with a wide range of functions and properties, including antibacterial, antioxidant, bioadhesive, and appropriate mechanical properties. Two approaches can be used for development of multifunctional hydrogel-based dressings; taking the advantages of the chemical composition of biomaterials and addition of nanomaterials or nanostructures. A large number of synthetic and natural polymers, bioactive molecules, or nanomaterials have been used to obtain hydrogel-based dressings with multifunctionality for wound healing applications. In the present review paper, advances in the development of multifunctional hydrogel-based dressings for wound healing have been highlighted.

Amniotic Membrane-Derived Mesenchymal Stem Cells for Heart Failure: A Systematic Review and Meta-Analysis of the Published Preclinical Studies.

Background: Ischemic cardiomyopathies are the leading causes of mortality and morbidity. Stem cell therapy using amniotic membrane mesenchymal stem cells have emerged as a promising cardiac regeneration modality. They have shown great immunological advantage when used in allogeneic or xenogeneic transplantation. The aim of the current study is to accumulate evidence from published preclinical studies on the application of amniotic membrane derived mesenchymal stem cells (AMSCs) in the treatment of ischemic cardiomyopathies including myocardial ischemia and heart failure. The aim is to define if there is enough high-quality current evidence to support starting the use of these cells in clinical trials. Methods: PubMed, SCOPUS, EMBASE, and ISI Web of Science databases were searched without temporal and language restrictions. Data were extracted from selected studies. The primary outcomes were left ventricular ejection fraction (LVEF) and LV fibrosis. The risk of bias (ROB) assessment was performed using SYRCLE's ROB tool. After qualitative synthesis, provided that data meets the criteria for quantitative analysis, a meta-analysis was performed using Stata software V12 to investigate the heterogeneity of the data and to get an overall estimate of the effect size of the treatment on each outcome. Results: On primary search, 438 citations were retrieved. After screening, three studies were selected for quantitative analysis of each of the outcomes LVEF and LV fibrosis. Their administration in acute and chronic MI alleviates heart failure and improves LVEF (SMD=3.56, 95% CI: 2.24-4.87, I-squared=83.1%, p=0.003) and reduces infarct size (SMD= -4.41, 95% CI: (-5.68)-(-3.14), I-squared=79.0%, p=0.009). These observations were achieved in the acute MI model, HF following ischemia due to coronary artery stenosis and coronary artery occlusion with the early restoration of the perfusion. Conclusion: Present low and medium quality evidence from preclinical studies confirm the efficacy of the AMSCs in the preclinical models of acute MI and HF following ischemia due to coronary artery stenosis and permanent/temporary coronary artery occlusion. High-quality preclinical studies are indicated to bridge the gaps in translation of the current findings of AMSCs research for the treatment of patients with acute and chronic myocardial ischemia and heart failure.

Why does COVID-19 pathology have several clinical forms?

The outbreak of a new, potentially fatal virus, SARS-COV-2, which started in December 2019 in Wuhan, China, and since developed into a pandemic has stimulated research for an effective treatment and vaccine. For this research to be successful, it is necessary to understand the pathology of the virus. So far, we know that this virus can harm different organs of the body. Although the exact mechanisms are still unknown, this phenomenon may result from the body's secretion of prostaglandin E2 (PGE2), which is involved in several inflammation and immunity pathways. Noticeably, the expression of this molecule can lead to a cytokine storm causing a variety of side effects. In this paper, we discuss those side effects in SARS-COV-2 infection separately to determine whether PGE2 is, indeed, an important causative factor. Lastly, we propose a mechanism by which PGE2 production increases in response to COVID-19 disease and suggest the possible direct relation between PGE2 levels and the severity of this disease. Also see the video abstract here: https://youtu.be/SnPFAcjxxKw.

Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review.

The nervous system, which consists of a complex network of millions of neurons, is one of the most highly intricate systems in the body. This complex network is responsible for the physiological and cognitive functions of the human body. Following injuries or degenerative diseases, damage to the nervous system is overwhelming because of its complexity and its limited regeneration capacity. However, neural tissue engineering currently has some capacities for repairing nerve deficits and promoting neural regeneration, with more developments in the future. Nevertheless, controlling the guidance of stem cell proliferation and differentiation is a challenging step towards this goal. Nanomaterials have the potential for the guidance of the stem cells towards the neural lineage which can overcome the pitfalls of the classical methods since they provide a unique microenvironment that facilitates cell-matrix and cell-cell interaction, and they can manipulate the cell signaling mechanisms to control stem cells' fate. In this article, the suitable cell sources and microenvironment cues for neuronal tissue engineering were examined. Afterward, the nanomaterials that impact stem cell proliferation and differentiation towards neuronal lineage were reviewed.