A new vision of the efficacy of both CAR-NK and CAR-T cells in treating cancers and autoimmune diseases.

Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells. Genetic modification of these cells provides a dual approach to the treatment of AD and cancer. It can be used through both CAR-independent and CAR-dependent mechanisms. The use of CAR-based cell therapies has been successful in treating cancer patients, leading to further investigation of this innovative treatment for alternative diseases, including AD. The complementary roles of CAR T and CAR NK cells have stimulated exploration in this area. Our study examines the latest research on the therapeutic effectiveness of these cells in treating both cancer and ADs.

Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: An animal study.

AIM: This study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. MATERIALS AND METHODS: Eighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. RESULTS: The average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. CONCLUSION: Metformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

Revolutionizing Infection Control: Harnessing MXene-Based Nanostructures for Versatile Antimicrobial Strategies and Healthcare Advancements.

The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques. Crucial characterization techniques such as XRD, Raman spectroscopy, SEM/TEM, FTIR, XPS, and BET analysis provide insightful structural and functional attributes. The review highlights MXenes' diverse antimicrobial mechanisms, spanning membrane disruption and oxidative stress induction, demonstrating efficacy against bacterial, viral, and fungal infections. Despite translational hurdles, MXene-based nanostructures offer broad-spectrum antimicrobial potential, with applications in drug delivery and diagnostics, presenting a promising path for advancing infection control in global healthcare.

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke.

Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self-regeneration, immunomodulation, and multi-potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC-based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naïve MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting-edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke-induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed.

Advances in microscopy characterization techniques for lipid nanocarriers in drug delivery: a comprehensive review.

This review paper provides an in-depth analysis of the significance of lipid nanocarriers in drug delivery and the crucial role of characterization techniques. It explores various types of lipid nanocarriers and their applications, emphasizing the importance of microscopy-based characterization methods such as light microscopy, confocal microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The paper also delves into sample preparation, quantitative analysis, challenges, and future directions in the field. The review concludes by underlining the pivotal role of microscopy-based characterization in advancing lipid nanocarrier research and drug delivery technologies.

The role of long noncoding RNA DGCR5 in cancers: Focus on molecular targets.

Long noncoding RNAs (lncRNAs) are major components of cellular transcripts that are emerging as important players in various biological pathways. Due to their specific expression and functional diversity in a variety of cancers, lncRNAs have promising applications in cancer diagnosis, prognosis, and therapy. Studies have shown that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) with high specificity and accuracy has the potential to become biomarkers in cancers. LncRNA DGCR5 can be noninvasively extracted from body fluids, tissues, and cells, and can be used as independent or auxiliary biomarkers to improve the accuracy of diagnosis or prognosis. Now, the underlying mechanisms of lncRNAs such as DGCR5 were explored as therapeutic targets, which have been investigated in clinical trials of several cancers. The DGCR5 lacks an appropriate animal model, which is necessary to gain greater knowledge of their functions. While some studies on the uses of DGCR5 have been carried out, the small sample size makes them unreliable. In this review, we presented a compilation of recent publications addressing the potential of lncRNA DGCR5 that could be considered as biomarkers or therapeutic targets, with the hopes of providing promised implications for future cancer therapy.

Recent advances in mRNA-based vaccine for cancer therapy; bench to bedside.

The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to a clinical reality over the last few decades. Compared to conventional vaccination methods, these vaccines have a number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up to now due to worries about the erratic and ineffective circulation of mRNA in vivo. Thankfully, these worries have largely been allayed by recent technological developments, which have led to the creation of multiple mRNA vaccination platforms for cancer and viral infections. The mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. The paper will examine the present status of mRNA vaccine technology and suggest future paths for the advancement and application of this exciting vaccine platform as a common therapeutic choice.

Intracranial Aneurysm in Pediatric Population: A Single-Center Experience.

PURPOSE: Pediatric intracranial aneurysms (PIA) are rarer and more complex when compared to adult aneurysms. In general, the clinical presentation of PIA is due to a mass effect, but the presenting symptoms can be also related to ischemia, subarachnoid hemorrhage (SAH), or in a combination of different symptoms. This paper aimed to report a single-center experience with clinical and angiographic aspects of brain aneurysm in children. METHODS: We retrospectively reviewed our prospectively maintained database for patients with intracranial aneurysms in our institution from July 2015 to February 2021. Among these, all patients under 18 years of age submitted to a diagnostic or therapeutic procedure for an intracranial aneurysm were included. RESULTS: Twelve patients were submitted to diagnostic or therapeutic procedures in our department. Three of them had multiple aneurysms, and in total, 17 intracranial aneurysms were assessed in this study. The most frequent location was in the middle cerebral artery (7 cases/41%). Five out of twelve children (42%) presented SAH due to ruptured aneurysm. Three patients (25%) had symptoms due to the mass effect from large aneurysms, with compression of cranial nerves or brainstem. Aneurysms diameters ranged from 1.5 mm to 34 mm (mean 14.2 mm), with six aneurysms being giant and eight being nonsaccular/fusiform. Twelve aneurysms were submitted to endovascular treatment, with one treatment-related clinical complication and later death. CONCLUSION: PIAs are rare diseases that can arise from a variety of different underlying pathological mechanisms. The management of these conditions requires a detailed understanding of the pathology and a multidisciplinary approach. Despite the availability of new technologies, parent vessel occlusion remains a valid option for aneurysms in the pediatric population.

WEB device for treatment of posterior communicating artery aneurysms.

BACKGROUND: Woven EndoBridge (WEB) device treatment of wide-neck bifurcation aneurysms has proved to be safe and effective, but the use of these devices in sidewall aneurysms has been reported only in a small number of case series. OBJECTIVE: To report our results in a cohort of consecutive patients in whom a WEB device was used as first-line treatment for posterior communicating artery (PComA) aneurysms. METHODS: We conducted a retrospective analysis of a prospectively maintained database of PComA aneurysms treated with a WEB device in our institution from June 1, 2012 to November 15, 2020. Clinical and radiological findings were evaluated at immediate and last follow-up. RESULTS: A total of 219 aneurysms were treated with a WEB device, including 15 PComA aneurysms in 15 patients, 10 of which were ruptured. Aneurysms were wide necked, with a mean aspect ratio of 1.6 (range 0.7-3.0) and a mean neck size of 4.2 mm (range 2.6-7.4 mm). No intraoperative rupture occurred and only one thromboembolic event was noted. Among the group with at least a 3-month digital subtraction angiography (DSA) follow-up, complete and adequate occlusion were obtained in 54% and 72%, respectively (average follow-up 13 months). Re-treatment was needed for two initially ruptured aneurysms. No procedure-related morbidity or mortality was reported. CONCLUSION: This series suggests the high safety profile of WEB devices even when used in off-label indications. Treatment with these devices seems to be a valuable strategy for ruptured wide-neck PComA aneurysms, avoiding the need for antiplatelet medication. However, occlusion rates should be investigated in further larger studies.

Proteomic Characterization, Biodistribution, and Functional Studies of Immune-Therapeutic Exosomes: Implications for Inflammatory Lung Diseases.

Dendritic cell (DC)-derived exosomes (DC EXO), natural nanoparticles of endosomal origin, are under intense scrutiny in clinical trials for various inflammatory diseases. DC EXO are eobiotic, meaning they are well-tolerated by the host; moreover, they can be custom-tailored for immune-regulatory or -stimulatory functions, thus presenting attractive opportunities for immune therapy. Previously we documented the efficacy of immunoregulatory DCs EXO (regDCs EXO) as immunotherapy for inflammatory bone disease, in an in-vivo model. We showed a key role for encapsulated TGFß1 in promoting a bone sparing immune response. However, the on- and off-target effects of these therapeutic regDC EXO and how target signaling in acceptor cells is activated is unclear. In the present report, therapeutic regDC EXO were analyzed by high throughput proteomics, with non-therapeutic EXO from immature DCs and mature DCs as controls, to identify shared and distinct proteins and potential off-target proteins, as corroborated by immunoblot. The predominant expression in regDC EXO of immunoregulatory proteins as well as proteins involved in trafficking from the circulation to peripheral tissues, cell surface binding, and transmigration, prompted us to investigate how these DC EXO are biodistributed to major organs after intravenous injection. Live animal imaging showed preferential accumulation of regDCs EXO in the lungs, followed by spleen and liver tissue. In addition, TGFß1 in regDCs EXO sustained downstream signaling in acceptor DCs. Blocking experiments suggested that sustaining TGFß1 signaling require initial interaction of regDCs EXO with TGFß1R followed by internalization of regDCs EXO with TGFß1-TGFß1R complex. Finally, these regDCs EXO that contain immunoregulatory cargo and showed biodistribution to lungs could downregulate the main severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target receptor, ACE2 on recipient lung parenchymal cells via TGFß1 in-vitro. In conclusion, these results in mice may have important immunotherapeutic implications for lung inflammatory disorders.

Difference in soft tissue response between immediate and delayed delivery suggests a new mechanism for recombinant human bone morphogenetic protein 2 action in large segmental bone defects.

The ability of recombinant human bone morphogenetic protein 2 on absorbable collagen sponge (rhBMP2/ACS) to regenerate bone in segmental defect has been well characterized. However, clinical results of rhBMP2/ACS constructs in secondary reconstruction of large mandibular and craniofacial defects have not been consistent. We hypothesized that rhBMP2 delivery triggers an endogenous response in the soft tissues surrounding the defect, in the form of expression of BMP2 and vascular endothelial growth factor (VEGF). Such osteogenic response will occur only after immediate, as opposed to delayed, rhBMP2 delivery, suggesting a new explanation to the difference in bone regeneration between the two settings. A 35-mm segmental bone and periosteum defect was created on one side of the mandible in 16 dogs divided in three groups. Group 1 (Gp1, n=6) ACS was loaded with 8 mL of rhBMP2 (0.2 mg/mL). In Gp2 (n=5) the same dose of rhBMP2/ACS was delivered into the defect 4 weeks after surgery. In Gp3 (control; n=5) the defect was reconstructed using ACS loaded with 8 mL of buffer only (devoid of rhBMP2). Tissues were collected after 12 weeks of reconstruction in all groups. Direct measurement of physical dimensions of regenerates and bone morphometry was performed to evaluate bone regeneration. The mRNA expression of both BMP2 and VEGF in the soft tissue surrounding the defect was evaluated using real-time quantitative PCR. Both BMP2 and VEGF proteins were quantified in immunostained sections. Immunoflurescence colocalization of BMP2 and acetylated low density lipoprotein (AcLDL) was done to detect the source of BMP2. Immediate delivery yielded better bone regeneration. Both BMP2 and VEGF mRNA expression was upregulated only in Gp1 (+7.3, p=0.001; +1.53, p=0.001, respectively). BMP2 protein was significantly higher in the immediate reconstruction group; however, VEGF protein was undetected in the examined sections. Immediate delivery of rhBMP2 seemed to induce endogenous release of BMP2 from the surrounding soft tissues, an effect that was lacking in delayed delivery and may explain the variability of clinical results associated with BMP2 use. Colocalization of BMP2 and endothelial cells (ECs) suggested that ECs could be the source of endogenous BMP2.