RESUMO
Male infertility is a significant global issue affecting 60-80 million people, with 40%-50% of cases linked to male issues. Exposure to radiation, drugs, sickness, the environment, and oxidative stress may result in testicular degeneration. Carbohydrate-based polymers (CBPs) restore testis differentiation and downregulate apoptosis genes. CBP has biodegradability, low cost, and wide availability, but is at risk of contamination and variations. CBP shows promise in wound healing, but more research is required before implementation in healthcare. Herein, we discuss the recent advances in engineering applications of CBP employed as scaffolds, drug delivery systems, immunomodulation, and stem cell therapy for testicular regeneration. Moreover, we emphasize the promising challenges warranted for future perspectives.
Assuntos
Polímeros , Testículo , Humanos , Masculino , Animais , Polímeros/química , Regeneração , Carboidratos/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Sistemas de Liberação de MedicamentosRESUMO
Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.
Assuntos
Imunoterapia Adotiva , Lipídeos , Nanopartículas , Receptores de Antígenos Quiméricos , Nanopartículas/química , Humanos , Imunoterapia Adotiva/métodos , Animais , Lipídeos/química , Linfócitos T/imunologia , Neoplasias/terapia , Neoplasias/imunologia , LipossomosRESUMO
Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5 g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160 mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5 ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.
RESUMO
Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.
RESUMO
Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.
RESUMO
Extracellular vesicles (EVs) are membrane-derived messengers which have been playing an important role in the inflammation and pathogenesis of lung diseases. EVs contain varieties of DNA, RNA, and membrane receptors through which they work as a delivery system for bioactive molecules as well as intracellular communicators. EV signaling mediates tumor progression and metastasis. EVs are linked with many diseases and perform a diagnostic role in lung injury and inflammation so are used to diagnose the severity of diseases. EVs containing a variety of biomolecules communicate with the recipient cells during pathophysiological mechanisms thereby acquiring the attention of clinicians toward the diagnostic and therapeutic potential of EVs in different lung diseases. In this review, we summarize the role of EVs in inflammation with an emphasis on their potential as a novel candidate in the diagnostics and therapeutics of chronic obstructive pulmonary disease, asthma, and sarcoidosis.
Assuntos
Vesículas Extracelulares , Lesão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Humanos , Inflamação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , PulmãoRESUMO
Extracellular vehicles (EVs) have been involved in several aspects of pregnancy, including endometrial receptivity, embryo implantation, and embryo-maternal communication showing them associated with pregnancy disorders, such as preeclampsia, gestational diabetes mellitus, and preterm birth. Further research is warranted to fully comprehend the exact pathophysiological roles of EVs and to develop new therapies targeting EVs thereby improving pregnancy outcomes. Herein, we review the recent knowledge on the multifaceted roles of EVs during pregnancy and address the majority of the molecular interactions between EVs, maternal, and fetal cells with an emphasis on disorders of pregnancy under the influence of EVs. Moreover, we also discuss its applications in clinical trials followed by prospects.
Assuntos
Vesículas Extracelulares , Humanos , Gravidez , Vesículas Extracelulares/metabolismo , Feminino , Animais , Complicações na Gravidez/metabolismo , Complicações na Gravidez/terapia , Implantação do Embrião/fisiologiaRESUMO
Tripartite motif (TRIM) family members participate in a variety of cellular activities, such as intracellular signaling, development, cellular death, protein quality control, immunological defense, waste degradation, and the emergence of cancer. These proteins usually act as E3 ubiquitin ligase. The final line of resistance against infectious viruses is a cytosolic ubiquitin ligase and antibody receptor called TRIM containing 21. TRIM21, a protein with a tripartite structure, has been linked to autoimmune erythematosus, Sjogren's disorder, and innate immunity. TRIM21 may either promote the formation of specific cancer-activating proteins, resulting in their proteasomal degradation, or it may do neither, depending on the kind of cancer and cancer-causing trigger. The current research has shown that the antiviral action of TRIM mostly depends on their role as E3-ubiquitin ligases and a significant portion of the TRIM family mediates the transmission of innate immune cell signals and the subsequent production of cytokines. We highlighted the function of TRIM family members in various inflammatory diseases.
RESUMO
Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies.