Development of an efficient hemostatic material based on cuttlefish ink nanoparticles loaded in cuttlebone biocomposite.

Traumatic hemorrhage is one of the main causes of mortality in civilian and military accidents. This study aimed to evaluate the effectiveness of cuttlefish bone (cuttlebone, CB) and CB loaded with cuttlefish ink (CB-CFI) nanoparticles for hemorrhage control. CB and CB-CFI were prepared and characterized using different methods. The hemostasis behavior of constructed biocomposites was investigated in vitro and in vivo using a rat model. Results showed that CFI nanoparticles (NPs) are uniformly dispersed throughout the CB surface. CB-CFI10 (10 mg CFI in 1.0 g of CB) showed the best blood clotting performance in both in vitro and in vivo tests. In vitro findings revealed that the blood clotting time of CB, CFI, and CB-CFI10 was found to be 275.4 ± 12.4 s, 229.9 ± 19.9 s, and 144.0 ± 17.5 s, respectively. The bleeding time in rat liver injury treated with CB, CFI, and CB-CFI10 was 158.1 ± 9.2 s, 114.0 ± 5.7 s, and 46.8 ± 2.7 s, respectively. CB-CFI10 composite resulted in more reduction of aPTT (11.31 ± 1.51 s) in comparison with CB (17.34 ± 2.12 s) and CFI (16.79 ± 1.46 s) (p < 0.05). Furthermore, CB and CB-CFI10 exhibited excellent hemocompatibility. The CB and CB-CFI did not show any cytotoxicity on human foreskin fibroblast (HFF) cells. The CB-CFI has a negative surface charge and may activate coagulation factors through direct contact with their components, including CaCO3, chitin, and CFI-NPs with blood. Thus, the superior hemostatic potential, low cost, abundant, simple, and time-saving preparation process make CB-CFI a very favorable hemostatic material for traumatic bleeding control in clinical applications.

CAR T therapies in multiple myeloma: unleashing the future.

In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with potent complement-dependent cytotoxic effects. Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory MM (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating MM, shedding light on their potential, limitations, and strategies employed to enhance their efficacy.

The role of key biomarkers in lymphatic malformation: An updated review.

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways.

Nanoparticles Containing Oxaliplatin and the Treatment of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly widespread malignancy and ranks as the second most common cause of cancer-related mortality. OBJECTIVE: Cancer patients, including those with CRC, who undergo chemotherapy, are often treated with platinum- based anticancer drugs such as oxaliplatin (OXA). Nevertheless, the administration of OXA is associated with a range of gastrointestinal problems, neuropathy, and respiratory tract infections. Hence, it is necessary to devise a potential strategy that can effectively tackle these aforementioned challenges. The use of nanocarriers has shown great potential in cancer treatment due to their ability to minimize side effects, target drugs directly to cancer cells, and improve drug efficacy. Furthermore, numerous studies have been published regarding the therapeutic efficacy of nanoparticles in the management of colorectal cancer. METHODS: In this review, we present the most relevant nanostructures used for OXA encapsulation in recent years, such as solid lipid nanoparticles, liposomes, polysaccharides, proteins, silica nanoparticles, metal nanoparticles, and synthetic polymer-carriers. Additionally, the paper provides a summary of the disadvantages and limits associated with nanoparticles. RESULTS: The use of different carriers for the delivery of oxaliplatin increased the efficiency and reduced the side effects of the drug. It has been observed that the majority of research investigations have focused on liposomes and polysaccharides. CONCLUSION: This potentially auspicious method has the potential to enhance results and enhance the quality of life for cancer patients undergoing chemotherapy. However, additional investigation is required to ascertain the most suitable medium for the transportation of oxaliplatin and to assess its efficacy through clinical trials.

MicroRNAs Regulate Inhibitor of Apoptosis Proteins (IAPs) in Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer mortality, with approximately 1.9 million new cases and 0.9 million deaths globally in 2020. One of the potential ways to treat colorectal cancer may be through the use of molecular methods to induce cell apoptosis. Apoptosis is a natural cellular event that regulates the growth and proliferation of body cells and prevents cancer. In this pathway, several molecules are involved; one group promotes this process, and some molecules that are representative of inhibitors of apoptosis proteins (IAPs) inhibit apoptosis. The most important human IAPs include c-IAP1, c-IAP2, NAIP, Survivin, XIAP, Bruce, ILP-2, and Livin. Several studies have shown that the inhibition of IAPs may be useful in cancer treatment. MicroRNAs (miRNAs) may be effective in regulating the expression of various proteins, including those of the IAPs family; they are a large subgroup of non-coding RNAs that are evolutionarily conserved. Therefore, in this review, the miRNAs that may be used to target IAPs in colorectal cancer were discussed.

Poly(aniline-co-melamine)@MnFe2O4 nanocatalyst for the synthesis of 4,4'-(arylmethylene) bis (1H-pyrazole-5-ol) derivatives, and 1,4- dihydropyrano[2,3-c]pyrazoles and evaluation of their antioxidant, and anticancer activities.

In this work, magnetic poly(aniline-co-melamine) nanocomposite as an efficient heterogeneous polymer-based nanocatalyst was fabricated in two steps. First, poly(aniline-co-melamine) was synthesized through the chemical oxidation by ammonium persulfate, then the magnetic nanocatalyst was successfully prepared from the in-situ coprecipitation method in the presence of poly(aniline-co-melamine). The resulting poly(aniline-co-melamine)@MnFe2O4 was characterized by FTIR, FESEM, XRD, VSM, EDX, TGA, and UV-vis analyses. The catalytic activity of poly(aniline-co-melamine)@MnFe2O4 was investigated in the synthesis of 4,4'-(arylmethylene)bis(1H-pyrazole-5-ol) derivatives, and new alkylene bridging bis 4,4'-(arylmethylene)bis(1H-pyrazole-5-ol) derivatives in excellent yields. The yield of 1,4-dihydropyrano[2,3-c]pyrazoles, 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol), yields, and new alkylene bridging bis 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives were obtained 89%-96%, 90%-96%, and 92%-96%, respectively. The poly(aniline-co-melamine)@MnFe2O4 nanocatalyst can be recycled without pre-activation and reloaded up to five consecutive runs without a significant decrease in its efficiency. In addition, the antioxidant activity of some derivatives was evaluated by DPPH assay. Results showed that the maximum antioxidant activity of 4,4'-(arylmethylene)bis(1H-pyrazole-5-ol) derivatives and 1,4-dihydropyrano[2,3-c]pyrazoles were 75% and 90%, respectively. Furthermore, 4,4'-(arylmethylene)bis(1H-pyrazole-5-ol) derivatives and 1,4-dihydropyrano[2,3-c]pyrazoles showed good potential for destroying colon cancer cell lines. Consequently, the poly(aniline-co-melamine)@MnFe2O4 nanocomposite is an excellent catalyst for green chemical processes owing to its high catalytic activity, stability, and reusability.

Aptamer-conjugated nanoliposomes containing COL1A1 siRNA sensitize CRC cells to conventional chemotherapeutic drugs.

COL1A1 is an important extracellular matrix component that is associated with poor prognosis in cancers. In this study, As1411 aptamer-conjugated liposomes were used for targeted siRNA delivery against the COL1A1 gene in colorectal cancer (CRC) cells. Cationic liposomes were synthesized and siRNA loading and conjugation of aptamer were confirmed by gel shift assay and spectrophotometry method. Release of siRNA from liposomes was assessed using dialysis method. Binding and uptake of aptamer-conjugated liposomes to and into cancer cells was assessed by fluorescence microscopy and flowcytometry. Gene expression was evaluated using qRT-PCR. Cell viability, chemosensitivity and apoptosis were determined by MTT assay and Annexin/PI kit. Cellular studies showed that liposomal transfer of COL1A1 siRNA into HCT116 and HEK293 cells significantly reduced the expression level of corresponding gen and cell viability, and significantly increased the sensitivity to chemotherapy drugs while free siRNA had no such effects. Aptamer conjugation was associated with increased cellular effects in HCT116 cells, but not in HEK293 cells. Our study revealed that delivery of COL1A1 siRNA via AS1411-targeted liposomes is a promising therapeutic approach to overcome treatment resistance in CRC.

Strontium doped bioglass incorporated hydrogel-based scaffold for amplified bone tissue regeneration.

Repairing of large bone injuries is an important problem in bone regeneration field. Thus, developing new therapeutic approaches such as tissue engineering using 3D scaffolds is necessary. Incorporation of some bioactive materials and trace elements can improve scaffold properties. We made chitosan/alginate/strontium-doped bioglass composite scaffolds with optimized properties for bone tissue engineering. Bioglass (BG) and Sr-doped bioglasses (Sr-BG) were synthesized using Sol-Gel method. Alginate-Chitosan (Alg/Cs) scaffold and scaffolds containing different ratio (10%, 20% and 30%) of BG (Alg/Cs/BG10, 20, 30) or Sr-BG (Alg/Cs/Sr-BG10, 20, 30) were fabricated using freeze drying method. Characterization of bioglasses/scaffolds was done using zeta sizer, FTIR, XRD, (FE) SEM and EDS. Also, mechanical strength, antibacterial effect degradation and swelling profile of scaffolds were evaluated. Bone differentiation efficiency and viability of MSCs on scaffolds were determined by Alizarin Red, ALP and MTT methods. Cell toxicity and antibacterial effect of bioglasses were determined using MTT, MIC and MBC methods. Incorporation of BG into Alg/Cs scaffolds amplified biomineralization and mechanical properties along with improved swelling ratio, degradation profile and cell differentiation. Mechanical strength and cell differentiation efficiency of Alg/Cs/BG20 scaffold was considerably higher than scaffolds with lower or higher BG concentrations. Alg/Cs/Sr-BG scaffolds had higher mechanical stability and more differentiation efficiency in comparison with Alg/Cs and Alg/Cs/BG scaffolds. Also, Mechanical strength and cell differentiation efficiency of Alg/Cs/Sr-BG20 scaffold was considerably higher than scaffolds with various Sr-BG concentrations. Biomineralization of Alg/Cs/BG scaffolds slightly was higher than Alg/Cs/Sr-BG scaffolds. Overall, we concluded that Alg/Cs/Sr-BG20 scaffolds are more suitable for repairing bone major injuries.

Binding Sites of Anticancer Drugs on Human Serum Albumin (HSA): A Review.

BACKGROUND: To recognize the action of pharmacologically approved anticancer drugs in biological systems, information regarding its pharmacokinetics, such as its transport within the plasma and delivery to its target site, is essential. In this study, we have tried to collect and present complete information about how these drugs bind to human serum albumin (HSA) protein. HSA functions as the main transport protein for an enormous variety of ligands in circulation and plays a vital role in the efficacy, metabolism, distribution, and elimination of these agents. METHODS: Therefore, this study includes information about the quenching constant, the binding constant obtained from Stern-Volmer and Hill equations, and molecular docking. RESULTS: Molecular docking was carried out to detect the binding models of HSA-anticancer drugs and the binding site of the drugs in HSA, which further revealed the contribution of amino acid residues of HSA in the drug complex binding. CONCLUSION: This review study showed that site I of the protein located in domain II can be considered the most critical binding site for anticancer drugs.

The Promise of CAR T-Cell Therapy for the Treatment of Cancer Stem Cells: A Short Review.

Chimeric antigen receptor (CAR) T-cell therapy is a type of sophisticated tailored immunotherapy used to treat a variety of tumors. Immunotherapy works by utilizing the body's own immune system to discover and destroy malignant cells. In CAR-T therapy, a patient's own immune cells are genetically engineered to recognize and attack cancer. Treatments employing CAR T-cells are currently showing promising therapeutic results in patients with hematologic malignancies, and their safety and feasibility in solid tumors have been verified. In this review, we will discuss in detail the likelihood that CAR Tcells inhibit cancer stem cells (CSCs) by selectively targeting their cell surface markers will ultimately improve the therapeutic response for patients with various forms of cancer. This review addresses the major components of cancer stem cell (CSC)-targeted CAR T-cells against malignancies, from bench to bedside.

Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study.

Acute lymphoblastic leukemia (ALL) is a cancer-specific lymphoid cell. Induction and consolidation chemotherapy alone or in combination with different therapeutic approaches remain the main treatment. Although complete or partial remission of the disease can be achieved, the risk of relapse or refractory leukemia is still high. More effective and safe therapy options are yet unmet needs. In recent years' new therapeutic approaches have been widely used. Hematopoietic Stem Cell Transplantation (HSCT) presents significant limitations and the outcome of the consolidation treatment is patient dependent. Side effects such as Graft versus Host Disease (GvHD) in allogeneic hematopoietic stem cell transplantation are extremely common, therefore, using alternative methods to address these challenges for treatment seems crucial. In the last decade, T cells genetically engineered with Chimeric Antigen Receptor (CAR) treatment for the ALL are largely studied and represent the new era of strategy. According to the Phase I/II clinical trials, this technology results seem very promising and can be used in the next future as an effective and safe treatment for ALL treatment. In this review different generations, challenges, and clinical studies related to chimeric antigen receptor (CAR) T-cells for ALL treatment are discussed.

FLVCR1-AS1 and FBXL19-AS1: Two Putative lncRNA Candidates in Multiple Human Cancers.

(1) Background: Mounting evidence supports the idea that one of the most critical agents in controlling gene expression could be long non-coding RNAs (lncRNAs). Upregulation of lncRNA is observed in the different processes related to pathologies, such as tumor occurrence and development. Among the crescent number of lncRNAs discovered, FLVCR1-AS1 and FBXL19-AS1 have been identified as oncogenes in many cancer progression and prognosis types, including cholangiocarcinoma, gastric cancer, glioma and glioblastoma, hepatocellular carcinoma, lung cancer, ovarian cancer, breast cancer, colorectal cancer, and osteosarcoma. Therefore, abnormal FBXL19-AS1 and FLVCR1-AS1 expression affect a variety of cellular activities, including metastasis, aggressiveness, and proliferation; (2) Methods: This study was searched via PubMed and Google Scholar databases until May 2022; (3) Results: FLVCR1-AS1 and FBXL19-AS1 participate in tumorigenesis and have an active role in impacting several signaling pathways that regulate cell proliferation, migration, invasion, metastasis, and EMT; (4) Conclusions: Our review focuses on the possible molecular mechanisms in a variety of cancers regulated by FLVCR1-AS1 and FBXL19-AS1. It is not surprising that there has been significant interest in the possibility that these lncRNAs might be used as biomarkers for diagnosis or as a target to improve a broader range of cancers in the future.

Identification of Key Gene Targets for Sensitizing Colorectal Cancer to Chemoradiation: an Integrative Network Analysis on Multiple Transcriptomics Data.

PURPOSE: Colorectal cancer (CRC) is a main cause of morbidity and mortality in the world. Chemoradioresistance is a major problem in CRC treatment. Identification of novel therapeutic targets in order to overcome treatment resistance in CRC is necessary. METHODS: In this study, gene expression omnibus (GEO) database was searched to find microarray datasets. Data normalization/analyzing was performed using ExAtlas. The gene ontology (GO) and pathway enrichment analysis was performed using g:Profiler. Protein-protein interaction network (PPIN) was constructed by Search Tool for the Retrieval of Interacting Genes (STRING) and analyzed using Cytoscape. Survival analysis was done using Kaplan-Meier curve method. RESULTS: Forty-one eligible datasets were included in study. A total of 12,244 differentially expressed genes (DEGs) and 7337 unique DEGs were identified. Among them, 1187 DEGs were overlapped in ≥ 3 datasets. Fifty-five overlapped genes were considered as hub genes. Common hub genes in chemo/radiation/chemoradiation datasets were chosen as the essential candidate genes (n = 13). Forty-one hub gene and 7 essential candidate genes were contributed in the significant modules. The modules were mainly enriched in the signaling pathways of senescence, autophagy, NF-κB, HIF-1, stem cell pluripotency, notch, neovascularization, cell cycle, p53, chemokine, and PI3K-Akt. NGFR, FGF2, and PROM1 genes were significantly predictors of CRC patient's survival. CONCLUSION: Our study revealed three-gene signatures as potential therapeutic targets and also candidate molecular markers in CRC chemoradioresistance.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers.

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

Investigating the relationship between the severity of coronary artery disease and inflammatory factors of MHR, PHR, NHR, and IL-25.

Background: Coronary artery disease (CAD), as a most common cause of death, is mainly caused by atherosclerosis. Due to the role of inflammation in the process of atherosclerosis, in the present study, the relationship between the severity of coronary artery disease and inflammatory factors of monocyte to HDL-C ratio (MHR), platelet-to-HDL-C ratio (PHR), neutrophil to HDL-C ratio (NHR), and IL-25 was investigated. Methods: In this cross-sectional study, 64 patients with diagnosis of coronary artery disease who were undergoing angiography in Farshchian heart center in Hamadan were studied. For each patient, the count of monocytes, neutrophils, platelet, and HDL-C, and IL-25 were measured from their blood and serum samples. Also, demographic information, such as age, gender, diabetes, smoking, and history of hypertension, was collected using a checklist. Data were described using frequency, percent, mean, and standard deviation. Statistical analysis was performed using independent t test, Mann-Whitney, Wilcoxon, and Spearman rank correlation tests, and multiple linear regression by SPSS version 25.0 SPSS Inc). P <.05 was considered as significant. Results: The results of this study showed that IL-25 and MHR index has a significant correlation with coronary artery disease and Gensini score (P ˂.001). The PHR index was associated with coronary artery disease. Also, qualitative variables, such as history of hypertension, history of smoking, and gender, have a significant association with the severity of coronary artery disease (P <.05). Conclusion: Among the inflammatory markers examined, IL-25 and MHR are stronger markers for assessing the severity of coronary artery disease. Simple and available IL-25 and MHR measurements may be able to, along with common risk factors and lipid profiles, predict the amount of vascular occlusion in treatment centers as an alternative of angiography as well as screening high risk patients prone to cardiovascular disease.

Could gene therapy cure HIV?

The Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) continues to be a major global public health issue, having claimed almost 33 million lives so far. According to the recent report of the World Health Organization (WHO) in 2019, about 38 million people are living with AIDS. Hence, finding a solution to overcome this life-threatening virus can save millions of lives. Scientists and medical doctors have prescribed HIV patients with specific drugs for many years. Methods such antiretroviral therapy (ART) or latency-reversing agents (LRAs) have been used for a while to treat HIV patients, however they have some side effects and drawbacks causing their application to be not quite successful. Instead, the application of gene therapy which refers to the utilization of the therapeutic delivery of nucleic acids into a patient's cells as a drug to treat disease has shown promising results to control HIV infection. Therefore, in this review, we will summarize recent advances in gene therapy approach against HIV.

Therapeutic Applications of Mesenchymal Stem Cells: A Comprehensive Review.

Mesenchymal Stem Cells (MSCs) are one of the most promising tools for cell therapy, that are isolated from bone marrow and many other adult tissues such as liver, cord blood, placenta, dental pulp and adipose tissue. Due to the lack of MHC class II expression on the surface of MSCs, they can also be used as a potent cell source for tissue regeneration in non-autologous cell therapy applications. Many advantages of MSCs such as their self-renewal, in vitro proliferation, rapid cell doubling capacity, anti-fibrotic, anti-apoptotic, anti-inflammatory, immunomodulatory and immunosuppressive effects, and also paracrine nature have been demonstrated in various pre-- clinical studies and clinical evidence. The ability of MSCs to differentiate into multiple cell lineages, as well as the lack of ethical issues in comparison with embryonic and induced Pluripotent Stem Cells (iPSCs), has introduced them as a suitable candidate for cell therapy. This review provides a comprehensive overview of various clinical trials based on MSCs for the treatment of a variety of diseases, demonstrating their capability in the treatment of dermatological, musculoskeletal, neurological, cardiovascular, respiratory, renal, gastroenterological and urological conditions, etc.

The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study.

In various cancers, high-grade tumor and poor survival rate in patients with upregulated lncRNAs UCA1 have been confirmed. Urothelial carcinoma associated 1 (UCA1) is an oncogenic non-coding RNA with a length of more than 200 nucleotides. The UCA1 regulate critical biological processes that are involved in cancer progression, including cancer cell growth, invasion, migration, metastasis, and angiogenesis. So It should not surprise that UCA1 overexpresses in variety of cancers type, including pancreatic cancer, ovarian cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, endometrial cancer, cervical cancer, bladder cancer, adrenal cancer, hypopharyngeal cancer, oral cancer, gallbladder cancer, nasopharyngeal cancer, laryngeal cancer, osteosarcoma, esophageal squamous cell carcinoma, renal cell carcinoma, cholangiocarcinoma, leukemia, glioma, thyroid cancer, medulloblastoma, hepatocellular carcinoma and multiple myeloma. In this article, we review the biological function and regulatory mechanism of UCA1 in several cancers and also, we will discuss the potential of its as cancer biomarker and cancer treatment.