Imaging Techniques and Biochemical Biomarkers: New Insights into Diagnosis of Pancreatic Cancer.

Pancreatic cancer (PaC) incidence is increasing, but our current screening and diagnostic strategies are not very effective. However, screening could be helpful in the case of PaC, as recent evidence shows that the disease progresses gradually. Unfortunately, there is no ideal screening method or program for detecting PaC in its early stages. Conventional imaging techniques, such as abdominal ultrasound, CT, MRI, and EUS, have not been successful in detecting early-stage PaC. On the other hand, biomarkers may be a more effective screening tool for PaC and have greater potential for further evaluation compared to imaging. Recent studies on biomarkers and artificial intelligence (AI)-enhanced imaging have shown promising results in the early diagnosis of PaC. In addition to proteins, non-coding RNAs are also being studied as potential biomarkers for PaC. This review consolidates the current literature on PaC screening modalities to provide an organized framework for future studies. While conventional imaging techniques have not been effective in detecting early-stage PaC, biomarkers and AI-enhanced imaging are promising avenues of research. Further studies on the use of biomarkers, particularly non-coding RNAs, in combination with imaging modalities may improve the accuracy of PaC screening and lead to earlier detection of this deadly disease.

Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.

The cell-surface receptor tyrosine kinase c-mesenchymal-epithelial transition factor (c-Met) is overexpressed in a wide range of solid tumors, making it an appropriate target antigen for the development of anticancer therapeutics. Various antitumor c-Met-targeting therapies (including monoclonal antibodies [mAbs] and tyrosine kinases) have been developed for the treatment of c-Met-overexpressing tumors, most of which have so far failed to enter the clinic because of their efficacy and complications. Antibody-drug conjugates (ADCs), a new emerging class of cancer therapeutic agents that harness the target specificity of mAbs to deliver highly potent small molecules to the tumor with the minimal damage to normal cells, could be an attractive therapeutic approach to circumvent these limitations in patients with c-Met-overexpressing tumors. Of great note, there are currently nine c-Met-targeting ADCs being examined in different phases of clinical studies as well as eight preclinical studies for treating various solid tumors. The purpose of this study is to present a broad overview of clinical- and preclinical-stage c-Met-targeting ADCs.

Integrating natural compounds and nanoparticle-based drug delivery systems: A novel strategy for enhanced efficacy and selectivity in cancer therapy.

Cancer remains a leading cause of death worldwide, necessitating the development of innovative and more effective treatment strategies. Conventional cancer treatments often suffer from limitations such as systemic toxicity, poor pharmacokinetics, and drug resistance. Recently, there has been growing attention to utilizing natural compounds derived from various sources as possible cancer therapeutics. Natural compounds have demonstrated diverse bioactive properties, including antioxidant, anti-inflammatory, and antitumor effects, making them attractive candidates for cancer treatment. However, their limited solubility and bioavailability present challenges for effective delivery to cancer cells. To overcome these limitations, researchers have turned to nanotechnology-based drug delivery systems. Nanoparticles, with their small size and unique properties, can encapsulate therapeutic agents and offer benefits such as improved solubility, prolonged drug release, enhanced cellular uptake, and targeted delivery. Functionalizing nanoparticles with specific ligands further enhances their precision in recognizing and binding to cancer cells. Combining natural compounds with nanotechnology holds great promise in achieving efficient and safe cancer treatments by enhancing bioavailability, pharmacokinetics, and selectivity toward cancer cells. This review article provides an overview of the advancements in utilizing natural substances and nanotechnology-based drug delivery systems for cancer treatment. It discusses the benefits and drawbacks of various types of nanoparticles, as well as the characteristics of natural compounds that make them appealing for cancer therapy. Additionally, current research on natural substances and nanoparticles in preclinical and clinical settings is highlighted. Finally, the challenges and future perspectives in developing natural compound-nanoparticle-based cancer therapies are discussed.

The therapeutic effects of berberine for gastrointestinal cancers.

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature-driven phytochemical component, is a well-known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers.

Comparison of the effects of preservation methods on structural, biological, and mechanical properties of the human amniotic membrane for medical applications.

Amniotic membrane (AM), the innermost layer of the placenta, is an exceptionally effective biomaterial with divers applications in clinical medicine. It possesses various biological functions, including scar reduction, anti-inflammatory properties, support for epithelialization, as well as anti-microbial, anti-fibrotic and angio-modulatory effects. Furthermore, its abundant availability, cost-effectiveness, and ethical acceptability make it a compelling biomaterial in the field of medicine. Given the potential unavailability of fresh tissue when needed, the preservation of AM is crucial to ensure a readily accessible and continuous supply for clinical use. However, preserving the properties of AM presents a significant challenge. Therefore, the establishment of standardized protocols for the collection and preservation of AM is vital to ensure optimal tissue quality and enhance patient safety. Various preservation methods, such as cryopreservation, lyophilization, and air-drying, have been employed over the years. However, identifying a preservation method that effectively safeguards AM properties remains an ongoing endeavor. This article aims to review and discuss different sterilization and preservation procedures for AM, as well as their impacts on its histological, physical, and biochemical characteristics.

MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis.

Gynecologic cancer is a significant cause of death in women worldwide, with cervical cancer, ovarian cancer, and endometrial cancer being among the most well-known types. The initiation and progression of gynecologic cancers involve a variety of biological functions, including angiogenesis and metastasis-given that death mostly occurs from metastatic tumors that have invaded the surrounding tissues. Therefore, understanding the molecular pathways underlying gynecologic cancer metastasis is critical for enhancing patient survival and outcomes. Recent research has revealed the contribution of numerous non-coding RNAs (ncRNAs) to metastasis and invasion of gynecologic cancer by affecting specific cellular pathways. This review focuses on three types of gynecologic cancer (ovarian, endometrial, and cervical) and three kinds of ncRNAs (long non-coding RNAs, microRNAs, and circular RNAs). We summarize the detailed role of non-coding RNAs in the different pathways and molecular interactions involved in the invasion and metastasis of these cancers.

Green Synthesis and Bioactivity of Aliphatic N-Substituted Glycine Derivatives.

Standard amino acids have an asymmetric α-carbon atom to which -COOH, -NH2, -H, and -R groups are bonded. Among them, glycine is the simplest (R = -H) with no asymmetric carbon, and other natural amino acids are C-substituted of glycine. Here, we have designed and made a green synthesis of some new N-substituted glycine derivatives with R-(NH)CH2-COOH formula, where R is flexible and hydrophobic with different chain lengths and benches of the type propyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl, 2-aminoheptyl, and octyl. These glycine derivatives were characterized by recording their melting points and FT-IR, mass, 1H NMR, and 13C NMR spectra. DFT studies revealed that 2-aminoheptyl glycine had the highest electronegativity value and can thus act as a good bidentate ligand for the metal centers. ADME comparative results and bioavailability radars indicated that both octyl- and 2-aminoheptyl glycine had the most lipophilicity, making them good agents in cell passing. Furthermore, lipophilicity determination showed that octyl glycine was the best and propylgly was more soluble than others. Based on solubility, lipophilicity, and dipole moment values, propyl- and 2-aminoheptyl-glycine were considered for bio-macromolecular interaction studies. Thus, the interaction of these two agents with DNA and HSA was studied using absorption spectroscopy and circular dichroism techniques. Due to the presence of the R-amine group, they can interact with the DNA by H-binding and hydrophobicity, while electrostatic mode could not be ruled out. Meanwhile, molecular docking studies revealed that octyl- and 2-aminoheptyl glycine had the highest negative docking energy, which reflects their higher tendency to interact with DNA. The DNA binding affinity of two candidate AAs was determined by viscosity measurement and fluorescence emission recording, which confirms that groove binding occurs. Also, the toxicity of these synthesized amino acid derivates was tested against the human foreskin fibroblast (HFF) cell line. They showed IC50 values within the range of 127-344 µM after 48 h with the highest toxicity for 2-aminoheptyl glycine.

Emerging roles of miR-145 in gastrointestinal cancers: A new paradigm.

Gastrointestinal (GI) carcinomas are a group of cancers affecting the GI tract and digestive organs, such as the gastric, liver, bile ducts, pancreas, small intestine, esophagus, colon, and rectum. MicroRNAs (miRNAs) are small functional non-coding RNAs (ncRNAs) which are involved in regulating the expression of multiple target genes; mainly at the post-transcriptional level, via complementary binding to their 3'-untranslated region (3'-UTR). Increasing evidence has shown that miRNAs have critical roles in modulating of various physiological and pathological cellular processes and regulating the occurrence and development of human malignancies. Among them, miR-145 is recognized for its anti-oncogenic properties in various cancers, including GI cancers. MiR-145 has been implicated in diverse biological processes of cancers through the regulation of target genes or signaling, including, proliferation, differentiation, tumorigenesis, angiogenesis, apoptosis, metastasis, and therapy resistance. In this review, we have summarized the role of miR-145 in selected GI cancers and also its downstream molecules and cellular processes targets, which could lead to a better understanding of the miR-145 in these cancers. In conclusion, we reveal the potential diagnostic, prognostic, and therapeutic value of miR-145 in GI cancer, and hope to provide new ideas for its application as a biomarker as well as a therapeutic target for the treatment of these cancer.

Laboratory methods: A concise review and update for COVID-19 diagnosis.

Since late December 2019, coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spread across the globe. The early, safe, sensitive, and accurate diagnosis of viral infection is required to decrease and control contagious infection and improve public health surveillance. The diagnosis generally is made by detecting SARS-CoV-2-related agents, including a range of nucleic acid detection-based, immunoassay-based, radiographic-based, and biosensor-based methods. This review presents the progress of various detection tools for diagnosing COVID-19 and addresses the advantages and restrictions of each detection method. Given that diagnosis of a contagious various like SARS-COV-2 can improve patient survival rates and break the transmission chain, there is no surprise that significant efforts should be made to reduce the limitations of tests that lead to false-negative results and to develop a substantial test for COVID-19 diagnosis.

Role of non-coding RNAs in neuroblastoma.

Neuroblastoma is known as the most prevalent extracranial malignancy in childhood with a neural crest origin. It has been widely accepted that non-coding RNAs (ncRNAs) play important roles in many types of cancer, including glioma and gastrointestinal cancers. They may regulate the cancer gene network. According to recent sequencing and profiling studies, ncRNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation. Disturbances in the expression of ncRNAs may act either as oncogenes or as anti-tumor suppressor genes, and can lead to the induction of cancer hallmarks. ncRNAs can be secreted from tumor cells inside exosomes, where they can be transferred to other cells to affect their function. However, these topics still need more study to clarify their exact roles, so the present review addresses different roles and functions of ncRNAs in neuroblastoma.

Non-coding RNAs and Exosomal Non-coding RNAs in Traumatic Brain Injury: the Small Player with Big Actions.

Nowadays, there is an increasing concern regarding traumatic brain injury (TBI) worldwide since substantial morbidity is observed after it, and the long-term consequences that are not yet fully recognized. A number of cellular pathways related to the secondary injury in brain have been identified, including free radical production (owing to mitochondrial dysfunction), excitotoxicity (regulated by excitatory neurotransmitters), apoptosis, and neuroinflammatory responses (as a result of activation of the immune system and central nervous system). In this context, non-coding RNAs (ncRNAs) maintain a fundamental contribution to post-transcriptional regulation. It has been shown that mammalian brains express high levels of ncRNAs that are involved in several brain physiological processes. Furthermore, altered levels of ncRNA expression have been found in those with traumatic as well non-traumatic brain injuries. The current review highlights the primary molecular mechanisms participated in TBI that describes the latest and novel results about changes and role of ncRNAs in TBI in both clinical and experimental research.

Exosomes released from U87 glioma cells treated with curcumin and/or temozolomide produce apoptosis in naive U87 cells.

Glioblastoma (GBM) remains the most lethal brain tumor without any curative treatment. Exosomes can mediate cell-to-cell communication, and may function as a new type of targeted therapy. In this study, the therapeutic benefits of exosomes generated by U87 cells treated with curcumin and/or temozolomide were investigated. The cells were cultured and treated with temozolomide (TMZ), curcumin (Cur), or their combination (TMZ+Cur). Exosomes were isolated with a centrifugation kit and characterized using DLS, SEM, TEM, and Western blotting. The levels of exosomal BDNF and TNF-α were measured. Naïve U87 cells were treated with the isolated exosomes, and the effects on apoptosis-related proteins HSP27, HSP70, HSP90, and P53 were assessed. All exosomes, Cur-Exo, TMZ-Exo, and TMZ+Cur-Exo increased cleaved caspase 3, Bax, and P53 proteins, while reducing HSP27, HSP70, HSP90, and Bcl2 proteins. Moreover all treatment groups increased apoptosis in naïve U87 recipient cells. Exosomes released from treated U87 cells had less BDNF and more TNF-α compared to exosomes released from naive U87 cells. In conclusion, we showed for the first time that exosomes released from drug-treated U87 cells could be a new therapeutic approach in glioblastoma, and could reduce the side effects produced by drugs alone. This concept needs to be further examined in animal models before clinical trials could be considered.

Clinical perspective: Antibody-drug conjugates for the treatment of HER2-positive breast cancer.

Antibody-drug conjugates (ADCs) are a promising class of cancer biopharmaceuticals that exploit the specificity of a monoclonal antibody (mAb) to selectively deliver highly cytotoxic small molecules to targeted cancer cells, leading to an enhanced therapeutic index through increased antitumor activity and decreased off-target toxicity. ADCs hold great promise for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after the approval and tremendous success of trastuzumab emtansine and trastuzumab deruxtecan, representing a turning point in both HER2-positive breast cancer treatment and ADC technology. Additionally and importantly, a total of 29 ADC candidates are now being investigated in different stages of clinical development for the treatment of HER2-positive breast cancer. The purpose of this review is to provide an insight into the ADC field in cancer treatment and present a comprehensive overview of ADCs approved or under clinical investigation for the treatment of HER2-positive breast cancer.

Rational approaches to discover SARS-CoV-2/ACE2 interaction inhibitors: Pharmacophore-based virtual screening, molecular docking, molecular dynamics and binding free energy studies.

The lack of effective treatment remains a bottleneck in combating the current coronavirus family pandemic, particularly coronavirus 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection of host cells by SARS-CoV-2 is mediated by the binding of its receptor-binding domain (RBD) on the spike (S) glycoprotein to the host angiotensin-converting enzyme (ACE2) receptor. As all developed and available vaccines against COVID-19 do not provide long-term immunity, the creation of an effective drug for the treatment of COVID-19 is necessary and cannot be ignored. Therefore, the aim of this study is to present a computational screening method to identify potential inhibitor candidates with a high probability of blocking the binding of RBD to the ACE2 receptor. Pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, and binding free-energy analyses were performed to identify potential inhibitor candidates against ACE2/SARS-CoV-2. In conclusion, we propose the compound PubChem-84280085 as a potential inhibitor of protein-protein interactions to disrupt the binding of the SARS-CoV-2-RBD to the ACE2 receptor.

Antiproliferative and apoptotic effects of conditioned medium released from human amniotic epithelial stem cells on breast and cervical cancer cells.

INTRODUCTION: Human amniotic membrane (hAM) and its cells have been proposed for several clinical applications, including cancer therapy. However, reports on the anticancer effects of human amniotic epithelial stem cells-conditioned media (hAECs-CM) are limited. This work aims to evaluate the anticancer effects of hAECs-CM on cervical cancer and breast cancer cell lines in vitro. METHODS: Human term placentas were gained from uncomplicated Cesarean sections from healthy donor women. After amnion peeling from the chorion, its epithelial stem cells were isolated and cultured, and its conditioned medium (CM) was collected for experiments. MTT assay was performed to assess cancer cells viability. Migration rate of cancer cells was examined via wound healing assay. Cell-cycle distribution and apoptosis were determined using flow cytometry. RESULTS: Based on MTT assay hAECs-CM was cytotoxic against cancerous cell lines in a dose-time-dependent manner. After 48 h of treatment with hAECs-CM pure, the cell viability of breast cancer cells includes MCF-7 and MDA-MB-231 reached to 73.2% and 65.5%, respectively. In the same situation, HeLa cervical cancer cell line revealed the lowest viability by 47.3%. The wound-healing assay displayed an incomplete wound closure of scratched MDA-MB-231 cells and significant inhibition of cell migration after hAECs-CM treatment. The results also revealed that hAECs-CM exerted anti-proliferation activity by prompting cell cycle arrest and apoptosis of cancer cells.Conclusions: hAECs-CM is a potent candidate for inducing apoptosis and simultaneously inhibition of the proliferation and migration of cancer cells via inhibiting cell cycle blockade.

Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment.

Glioblastoma (GBM) is the most frequent malignancy among primary brain tumors in adults and one of the worst 5-year survival rates (< 7%) among all human cancers. Till now, treatments that target particular cell or intracellular metabolism have not improved patients' survival. GBM recruits healthy brain cells and subverts their processes to create a microenvironment that contributes to supporting tumor progression. This microenvironment encompasses a complex network in which malignant cells interact with each other and with normal and immune cells to promote tumor proliferation, angiogenesis, metastasis, immune suppression, and treatment resistance. Communication can be direct via cell-to-cell contact, mainly through adhesion molecules, tunneling nanotubes, gap junctions, or indirect by conventional paracrine signaling by cytokine, neurotransmitter, and extracellular vesicles. Understanding these communication routes could open up new avenues for the treatment of this lethal tumor. Hence, therapeutic approaches based on glioma cells` communication have recently drawn attention. This review summarizes recent findings on the crosstalk between glioblastoma cells and their tumor microenvironment, and the impact of this conversation on glioblastoma progression. We also discuss the mechanism of communication of glioma cells and their importance as therapeutic targets and diagnostic and prognostic biomarkers. Overall, understanding the biological mechanism of specific interactions in the tumor microenvironment may help in predicting patient prognosis and developing novel therapeutic strategies to target GBM.

Unveiling diagnostic and therapeutic strategies for cervical cancer: biomarker discovery through proteomics approaches and exploring the role of cervical cancer stem cells.

Cervical cancer (CC) is a major global health problem and leading cause of cancer deaths among women worldwide. Early detection through screening programs has reduced mortality; however, screening compliance remains low. Identifying non-invasive biomarkers through proteomics for diagnosis and monitoring response to treatment could improve patient outcomes. Here we review recent proteomics studies which have uncovered biomarkers and potential drug targets for CC. Additionally, we explore into the role of cervical cancer stem cells and their potential implications in driving CC progression and therapy resistance. Although challenges remain, proteomics has the potential to revolutionize the field of cervical cancer research and improve patient outcomes.

Non-coding RNAs and glioma: Focus on cancer stem cells.

Glioblastoma and gliomas can have a wide range of histopathologic subtypes. These heterogeneous histologic phenotypes originate from tumor cells with the distinct functions of tumorigenesis and self-renewal, called glioma stem cells (GSCs). GSCs are characterized based on multi-layered epigenetic mechanisms, which control the expression of many genes. This epigenetic regulatory mechanism is often based on functional non-coding RNAs (ncRNAs). ncRNAs have become increasingly important in the pathogenesis of human cancer and work as oncogenes or tumor suppressors to regulate carcinogenesis and progression. These RNAs by being involved in chromatin remodeling and modification, transcriptional regulation, and alternative splicing of pre-mRNA, as well as mRNA stability and protein translation, play a key role in tumor development and progression. Numerous studies have been performed to try to understand the dysregulation pattern of these ncRNAs in tumors and cancer stem cells (CSCs), which show robust differentiation and self-regeneration capacity. This review provides recent findings on the role of ncRNAs in glioma development and progression, particularly their effects on CSCs, thus accelerating the clinical implementation of ncRNAs as promising tumor biomarkers and therapeutic targets.

Evidence for the Benefits of Melatonin in Cardiovascular Disease.

The pineal gland is a neuroendocrine gland which produces melatonin, a neuroendocrine hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity and neuroprotective properties. Numerous studies have shown that melatonin has significant functions in cardiovascular disease, and may have anti-aging properties. The ability of melatonin to decrease primary hypertension needs to be more extensively evaluated. Melatonin has shown significant benefits in reducing cardiac pathology, and preventing the death of cardiac muscle in response to ischemia-reperfusion in rodent species. Moreover, melatonin may also prevent the hypertrophy of the heart muscle under some circumstances, which in turn would lessen the development of heart failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent rodent studies have shown that melatonin acts as an anti-oxidant and is effective in suppressing heart damage mediated by pharmacologic drugs. Therefore, melatonin has been shown to have cardioprotective activity in multiple animal and human studies. Herein, we summarize the most established benefits of melatonin in the cardiovascular system with a focus on the molecular mechanisms of action.