Recent advances and applications of peptide-agent conjugates for targeting tumor cells.

BACKGROUND: Cancer, being a complex disease, presents a major challenge for the scientific and medical communities. Peptide therapeutics have played a significant role in different medical practices, including cancer treatment. METHOD: This review provides an overview of the current situation and potential development prospects of anticancer peptides (ACPs), with a particular focus on peptide vaccines and peptide-drug conjugates for cancer treatment. RESULTS: ACPs can be used directly as cytotoxic agents (molecularly targeted peptides) or can act as carriers (guiding missile) of chemotherapeutic agents and radionuclides by specifically targeting cancer cells. More than 60 natural and synthetic cationic peptides are approved in the USA and other major markets for the treatment of cancer and other diseases. Compared to traditional cancer treatments, peptides exhibit anticancer activity with high specificity and the ability to rapidly kill target cancer cells. ACP's target and kill cancer cells via different mechanisms, including membrane disruption, pore formation, induction of apoptosis, necrosis, autophagy, and regulation of the immune system. Modified peptides have been developed as carriers for drugs, vaccines, and peptide-drug conjugates, which have been evaluated in various phases of clinical trials for the treatment of different types of solid and leukemia cancer. CONCLUSIONS: This review highlights the potential of ACPs as a promising therapeutic option for cancer treatment, particularly through the use of peptide vaccines and peptide-drug conjugates. Despite the limitations of peptides, such as poor metabolic stability and low bioavailability, modified peptides show promise in addressing these challenges. Various mechanism of action of anticancer peptides. Modes of action against cancer cells including: inducing apoptosis by cytochrome c release, direct cell membrane lysis (necrosis), inhibiting angiogenesis, inducing autophagy-mediated cell death and immune cell regulation.

The Regulation, Functions, and Signaling of miR-153 in Neurological Disorders, and Its Potential as a Biomarker and Therapeutic Target.

Treatment of neurological disorders has always been one of the challenges facing scientists due to poor prognosis and symptom overlap, as well as the progress of the disease process. Neurological disorders such as Huntington's, Parkinson's, Alzheimer's diseases, and Amyotrophic Lateral Sclerosis are very debilitating. Therefore, finding a biomarker is essential for early diagnosis and treatment goals. Recent studies have focused more on molecular factors and gene manipulation to find effective diagnostic and therapeutic biomarkers. Among these factors, microRNAs (miRNAs/ miRs) have attracted much attention. On the other hand, a growing correlation between miRNAs and neurological disorders has caused scientists to consider it as a diagnostic and therapeutic target. In this line, the miR-153 is one of the most important and highly conserved miRNAs in mice and humans, whose expression level is not only altered in neurological disorders but also improves neurogenesis. MiR-153 can regulate multiple biological processes by targeting various factors. Furthermore, the miR-153 expression also can be regulated by important regulators, such as long non-coding RNAs (e.g., KCNQ1OT1) and some compounds (e.g., Tanshinone IIA) altering the expression of miR-153. Given the growing interest in miR-153 as a biomarker and therapeutic target for neurological diseases as well as the lack of comprehensive investigation of miR-153 function in these disorders, it is necessary to identify the downstream and upstream targets and also it's potential as a therapeutic biomarker target. In this review, we will discuss the critical role of miR-153 in neurological disorders for novel diagnostic and prognostic purposes and its role in multi-drug resistance.

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration.

BACKGROUND: Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model. METHODS: This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed. RESULTS: Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05). CONCLUSION: In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan.

The role of miR-153 and related upstream/downstream pathways in cancers: from a potential biomarker to treatment of tumor resistance and a therapeutic target.

MicroRNAs (miRNAs/miRs) are small non-coding RNAs that have a multifunction and play essential roles in gene regulation. Their dysregulation is associated with several human cancers. MiR-153 has a critical role in many biological processes, such as suppressing tumor growth (mostly), responses to treatment, and drug resistance. However, miR-153 in some cancers shows a different role as an oncogene, such as prostate. The miR-153 expression can be regulated by several regulators, such as lncRNAs and circular RNAs. By discovering the target factors for miR-153, it may be possible to approach early diagnosis, reversing drug resistance, and treatment of cancers. This will help choose the precise treatment for the patient and not incur additional costs in treatment. Thus, we attempt to summarize the current situation and potential development prospects about the role of miR-153 in cancers. The miR-153 paly an important role in cancers and can be used for diagnosis and prognosis.

New Insights into the Biosensing of Parkinson's Disease Biomarkers: A Concise Review.

BACKGROUND: Parkinson's disease (PD) is a long-term, degenerative, and neurological disease in which a person loses control of certain body functions. The formulation of novel effective therapeutics for PD as a neurodegenerative disease requires accurate and efficient diagnosis at the early stages. OBJECTIVE: Analyzing data gathered by measurable signals converted from biological reactions allows for qualitative and quantitative evaluations. Among various approaches reported so far, biosensors are powerful analytical tools that have been used in detecting the biomarkers of PD. METHODS: Biosensor's biological recognition components include antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, and biomimetic structures. This review introduces electrochemical, optical, and optochemical detection of PD biomarkers based on recent advances in nanotechnology and material science, which resulted in the development of high-performance biosensors in this field. RESULTS: PD biomarkers such as α-synuclein protein, dopamine (DA), urate, ascorbic acid, miRNAs, and their biological roles are summarized. Additionally, the advantages and disadvantages of the usual standard methods are reviewed. We compared electrochemical, optical, and optochemical biosensors' properties and novel strategies for higher sensitivity and selectivity. CONCLUSION: The development of novel biosensors is required for the early diagnosis of PD as sensitive, rapid, reliable, and cost-effective systems.

Age-Specific Differences in the Severity of COVID-19 Between Children and Adults: Reality and Reasons.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, children experience mild symptoms compared to adults. However, the precise explanations for this disparity are not clear. Thus, we attempted to identify rational explanations about age-related differences as reported in different studies. Given the incomplete data on SARS-CoV-2, some information has been gathered from other studies of earlier coronavirus or influenza outbreaks. Age-related differences in disease severity are important with regard to diagnosis, prognosis, and treatment of SARS-CoV-2 infections. In addition, these differences impact social distancing needs, since pediatric patients with mild or asymptomatic are likely to play a significant role in disease transmission.

Effects of transcranial direct current stimulation on cognitive dysfunction in multiple sclerosis.

BACKGROUND: Around 40%-70% of patients with multiple sclerosis (MS) may experience cognitive impairments during the course of their disease with detrimental effects on social and occupational activities. Transcranial direct current stimulation (tDCS has been investigated in pain, fatigue, and mood disorders related to MS, but to date, few studies have examined effects of tDCS on cognitive performance in MS. OBJECTIVE: The current study aimed to investigate the effects of a multi-session tDCS protocol on cognitive performance and resting-state brain electrical activities in patients with MS. METHODS: Twenty-four eligible MS patients were randomly assigned to real (anodal) or sham tDCS groups. Before and after 8 consecutive daily tDCS sessions over the left dorsolateral prefrontal cortex (DLPFC), patients' cognitive performance was assessed using the Cambridge Brain Sciences-Cognitive Platform (CBS-CP). Cortical electrical activity was also evaluated using quantitative electroencephalography (QEEG) analysis at baseline and after the intervention. RESULTS: Compared to the sham condition, significant improvement in reasoning and executive functions of the patients in the real tDCS group was observed. Attention was also improved considerably but not statistically significantly following real tDCS. However, no significant changes in resting-state brain activities were observed after stimulation in either group. CONCLUSION: Anodal tDCS over the left DLPFC appears to be a promising therapeutic option for cognitive dysfunction in patients with MS. Larger studies are required to confirm these findings and to investigate underlying neuronal mechanisms.