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.

A computational approach to design a multiepitope vaccine against H5N1 virus.

Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.

Molecular mechanism of lncRNAs in pathogenesis and diagnosis of auto-immune diseases, with a special focus on lncRNA-based therapeutic approaches.

Autoimmune diseases are a diverse set of conditions defined by organ damage due to abnormal innate and acquired immune system responses. The pathophysiology of autoimmune disorders is exceedingly intricate and has yet to be fully understood. The study of long non-coding RNAs (lncRNAs), non-protein-coding RNAs with at least 200 nucleotides in length, has gained significant attention due to the completion of the human genome project and the advancement of high-throughput genomic approaches. Recent research has demonstrated how lncRNA alters disease development to different degrees. Although lncRNA research has made significant progress in cancer and generative disorders, autoimmune illnesses are a relatively new research area. Moreover, lncRNAs play crucial functions in differentiating various immune cells, and their potential relationships with autoimmune diseases have received growing attention. Because of the importance of Th17/Treg axis in auto-immune disease development, in this review, we discuss various molecular mechanisms by which lncRNAs regulate the differentiation of Th17/Treg cells. Also, we reviewed recent findings regarding the several approaches in the application of lncRNAs in the diagnosis and treatment of human autoimmune diseases, as well as current challenges in lncRNA-based therapeutic approaches to auto-immune diseases.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight.

Diabetic foot ulcer (DFU) is considered the most catastrophic complication of diabetes mellitus (DM), leading to repeated hospitalizations, infection, gangrene, and finally amputation of the limb. In patients suffering from diabetes mellitus, the wound-healing process is impaired due to various factors such as endothelial dysfunction and synthesis of advanced glycation end-products, hence, conventional therapeutic interventions might not be effective. With increasing therapeutic applications of mesenchymal stem cells (MSCs) in recent years, their potential as a method for improving the wound-healing process has gained remarkable attention. In this field, mesenchymal stem cells exert their beneficial effects through immunomodulation, differentiation into the essential cells at the site of ulcers, and promoting angiogenesis, among others. In this article, we review cellular and molecular pathways through which mesenchymal stem cell therapy reinforces the healing process in non-healing Diabetic foot ulcers.

Quercetin and Glioma: Which Signaling Pathways are Involved?

Gliomas are the most common brain tumors. These tumors commonly exhibit continuous growth without invading surrounding brain tissues. Dominant remedial approaches suffer limited therapy and survival rates. Although some progress has been made in conventional glioma treatments, these breakthroughs have not yet proven sufficient for treating this malignancy. The remedial options are limited given gliomas' aggressive metastasis and drug resistance. Quercetin, a flavonoid, is an anti-oxidative, anti-allergic, antiviral, anti-inflammatory, and anticancer compound. Multiple lines of evidence have shown that Quercetin has anti-tumor effects, documenting this natural compound exerts its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, metastasis, and autophagy. Herein, we summarize various cellular and molecular pathways that are affected by Quercetin in gliomas.

Angiogenesis-related non-coding RNAs and gastrointestinal cancer.

Gastrointestinal (GI) cancers are among the main reasons for cancer death globally. The deadliest types of GI cancer include colon, stomach, and liver cancers. Multiple lines of evidence have shown that angiogenesis has a key role in the growth and metastasis of all GI tumors. Abnormal angiogenesis also has a critical role in many non-malignant diseases. Therefore, angiogenesis is considered to be an important target for improved cancer treatment. Despite much research, the mechanisms governing angiogenesis are not completely understood. Recently, it has been shown that angiogenesis-related non-coding RNAs (ncRNAs) could affect the development of angiogenesis in cancer cells and tumors. The broad family of ncRNAs, which include long non-coding RNAs, microRNAs, and circular RNAs, are related to the development, promotion, and metastasis of GI cancers, especially in angiogenesis. This review discusses the role of ncRNAs in mediating angiogenesis in various types of GI cancers and looks forward to the introduction of mimetics and antagonists as possible therapeutic agents.

Non-coding RNAs related to angiogenesis in gynecological cancer.

Gynecological cancer affects the female reproductive system, including ovarian, uterine, endometrial, cervical, vulvar, and vaginal tumors. Non-coding RNAs (ncRNAs), and in particular microRNAs, function as regulatory molecules, which can control gene expression in a post-transcriptional manner. Normal physiological processes like cellular proliferation, differentiation, and apoptosis, and pathological processes such as oncogenesis and metastasis are regulated by microRNAs. Numerous reports have shown a direct role of microRNAs in the modulation of angiogenesis in gynecological cancer, via targeting pro-angiogenic factors and signaling pathways. Understanding the molecular mechanism involved in the regulation of angiogenesis by microRNAs may lead to new treatment options. Recently the regulatory role of some long non-coding RNAs in gynecological cancer has also been explored, but the information on this function is more limited. The aim of this article is to explore the pathways responsible for angiogenesis, and to what extent ncRNAs may be employed as biomarkers or therapeutic targets in gynecological cancer.

Therapeutic Potential of Berberine in the Treatment of Glioma: Insights into Its Regulatory Mechanisms.

Glioma is known as one of the most common primary intracranial tumors accounting for four-fifths of malignant brain tumors. There are several biological pathways that play a synergistic, pathophysiological role in glioma, including apoptosis, autophagy, oxidative stress, and cell cycle arrest. According to previous rese arches, the drugs used in the treatment of glioma have been associated with significant limitations. Therefore, improved and/or new therapeutic platforms are required. In this regard, multiple flavonoids and alkaloids have been extensively studied in the treatment of glioma. Berberine is a protoberberine alkaloid with wide range of pharmacological activities, applicable to various pathological conditions. Few studies have reported beneficial roles of berberine in glioma. Berberine exerts its pharmacological functions in glioma by controlling different molecular and cellular pathways. We reviewed the existing knowledge supporting the use of berberine in the treatment of glioma and its effects on molecular and cellular mechanisms.

Gynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles.

Gynecologic cancers involve the female genital organs, such as the vulva, vagina, cervix, endometrium, ovaries, and fallopian tubes. The occurrence and frequency of gynecologic cancer depends on personal lifestyle, history of exposure to viruses or carcinogens, genetics, body shape, and geographical habitat. For a long time, research into the molecular biology of cancer was broadly restricted to protein-coding genes. Recently it has been realized that non-coding RNAs (ncRNA), including long noncoding RNAs (LncRNAs), microRNAs, circular RNAs and piRNAs (PIWI-interacting RNAs), can all play a role in the regulation of cellular function within gynecological cancer. It is now known that ncRNAs are able to play dual roles, i.e. can exert both oncogenic or tumor suppressive functions in gynecological cancer. Moreover, several clinical trials are underway looking at the biomarker and therapeutic roles of ncRNAs. These efforts may provide a new horizon for the diagnosis and treatment of gynecological cancer. Herein, we summarize some of the ncRNAs that have been shown to be important in gynecological cancers.

Autophagy in cancers including brain tumors: role of MicroRNAs.

Autophagy has a crucial role in many cancers, including brain tumors. Several types of endogenous molecules (e.g. microRNAs, AKT, PTEN, p53, EGFR, and NF1) can modulate the process of autophagy. Recently miRNAs (small non-coding RNAs) have been found to play a vital role in the regulation of different cellular and molecular processes, such as autophagy. Deregulation of these molecules is associated with the development and progression of different pathological conditions, including brain tumors. It was found that miRNAs are epigenetic regulators, which influence the level of proteins coded by the targeted mRNAs with any modification of the genetic sequences. It has been revealed that various miRNAs (e.g., miR-7-1-3p, miR-340, miR-17, miR-30a, miR-224-3p, and miR-93), as epigenetic regulators, can modulate autophagy pathways within brain tumors. A deeper understanding of the underlying molecular targets of miRNAs, and their function in autophagy pathways could contribute to the development of new treatment methods for patients with brain tumors. In this review, we summarize the various miRNAs, which are involved in regulating autophagy in brain tumors. Moreover, we highlight the role of miRNAs in autophagy-related pathways in different cancers. Video abstract.

Autophagy regulation by microRNAs: Novel insights into osteosarcoma therapy.

Osteosarcoma (OS) is a kind of primary bone cancer that is considered as the leading cause of children death. Surgery and chemotherapy are considered as common treatment approaches for OS; the rate of survival for patients is almost 60-70%. Besides the used therapeutic approaches, it seems that there is a crucial need to launch new treatments for OS. In this regard, more understanding about cellular and molecular pathways involved in OS can contribute to recovery and develop new therapeutic platforms. Autophagy is a cellular machinery that digests and degrades dysfunctional proteins and organelles, so it can regulate the cell proliferation and survival. Most of the time, OS cells use autophagy to increase their survival and proliferation and to gain the ability to resist chemotherapy. Although, there are several controversial evidences on how OS cells use autophagy. A variety of cellular and molecular pathways, that is, microRNAs (miRNAs) can modulate autophagy. MiRNAs are some endogenous, approximately 22 nucleotide RNAs that have an important role in posttranscriptional regulation of mRNAs by targeting them. There are many evidences that the various miRNA expressions in OS cells are dysregulated, so it can propel a normal cell to cancerous one by influencing the cell survival, apoptosis, and autophagy, and eventually increased chemoresitance. Hence, miRNAs can be considered as new biomarkers for OS diagnosis, and according to the role of autophagy in OS progression, miRNAs can use inhibiting or promoting autophagy agents. The present review summarizes the effects of aberrant expression of miRNAs in OS diagnosis and treatment with focus on their roles in autophagy.