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Nanomedicine has been developed to reduce or eliminate the side effects and toxicity upon systemic therapy of chemotherapeutic agents and to improve their therapeutic efficacy. However, the translation of non‐sized or nano‐encapsulated drugs is hampered by the low penetration and accumulation of engineered nanoparticles (NPs) in sites of tumors as well as their poor pharmacokinetics. This may be due to the synthetic structure of NPs and also complicated and unknown characteristics of the solid tumor microenvironment (TME). As a result, the TME is being better identified, and the interactions between NPs and the TME or human body are being discovered or predicted. These findings have led to the development of more biocompatible, intelligent, and controllable bio‐based nanoformulations that could overcome current barriers and provide sufficient drug delivery to the TME, as discussed in this paper. These formulations are designed to (i) modify the surface of NPs to improve blood circulation while reducing their off‐target accumulation and side effects in vivo, (ii) pass through the tumor vasculature by modulating or targeting angiogenesis, (iii) promote NPs distribution in solid tumor regions by applying biological/physical stimuli or extracellular matrix remodeling, and (iv) overcome the cell membrane barrier and other compartments of the cell by specific cell targeting to release the payload drug into the cytoplasm or nucleoplasm. [ABSTRACT FROM AUTHOR]

In this research, a novel and efficient nanocatalyst, namely, palladium immobilized onto 1,4-bis(pyrid-4-yl)benzene grafted to n-propyl-functionalized Fe3O4@MCM-41 nanoparticles (PBPBPMF), was synthesized and introduced. Then, its catalytic activity was tested in the synthesis of bis(pyrazolyl)methane (14 examples, 90–97%, 9–25 min, solvent-free, 60 °C) and biphenyl (13 examples, 80–98%, 10–120 min, PEG-400, 70 °C) derivatives. Bis(pyrazolyl)methane derivatives were synthesized via a one-pot pseudo-five-component reaction of aldehydes, ethyl acetoacetate, and phenylhydrazine, and biphenyl derivatives were obtained by a Stille coupling reaction. Transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), N2 sorption isotherms, vibrating sample magnetometer (VSM), inductively coupled plasma atomic emission spectrometer (ICP-OES), X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and elemental mapping analyses were used to identify the catalyst. The PBPBPMF is a heterogeneous catalyst with several advantages, including a large specific surface area, ease of purification, and separation from the reaction mixture; furthermore, the nanocatalyst was recycled six times without appreciably altering its catalytic properties. [ABSTRACT FROM AUTHOR]

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski's rule of 5, high binding affinity (highest binding affinity: -9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19. [ABSTRACT FROM AUTHOR]

Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are the main radiotherapy techniques for treating and managing rectal cancer. Collimator rotation is one of the crucial parameters in radiotherapy planning, and its alteration can cause dosimetric variations. This study assessed the effect of collimator rotation on the dosimetric results of various IMRT and VMAT plans for rectal cancer.Computed tomography (CT) images of 20 male patients with rectal cancer were utilized for IMRT and VMAT treatment planning with various collimator angles. Nine different IMRT techniques (5, 7, and 9 coplanar fields with collimator angles of 0°, 45°, and 90°) and six different VMAT techniques (1 and 2 full coplanar arcs with collimator angles of 0°, 45°, and 90°) were planned for each patient. The dosimetric results of various treatment techniques for target tissue (conformity index [CI] and homogeneity index [HI]) and organs at risk (OARs) sparing (parameters obtained from OARs dose–volume histograms [DVH]) as well as radiobiological findings were analyzed and compared.The 7-fields IMRT technique demonstrated lower bladder doses (V40Gy, V45Gy), unaffected by collimator rotation. The 9-fields IMRT and 2-arcs VMAT (excluding the 90-degree collimator) had the lowest V35Gy and V45Gy. A 90-degree collimator rotation in 2-arcs VMAT significantly increased small bowel and bladder V45Gy, femoral head doses, and HI values. Radiobiologically, the 90-degree rotation had adverse effects on small bowel NTCP (normal tissue complication probability). No superiority was found for a 45-degree collimator rotation over 0 or 30 degrees in VMAT techniques.Collimator rotation had minimal impact on dosimetric parameters in IMRT planning but is significant in VMAT techniques. A 90-degree rotation in VMAT, particularly in a 2-full arc technique, adversely affects PTV homogeneity index, bladder dose, and small bowel NTCP. Other evaluated collimator angles did not significantly affect VMAT dosimetrical or radiobiological outcomes. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease., Methods: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to April 20, 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates., Results: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192 to 1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13 to 1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036 to 2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091 to 1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193 to 6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events., Conclusion: Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CL pro ). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski's rule of 5, high binding affinity (highest binding affinity: -9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CL pro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Prabhakaran, Hebbani, Menon, Paital, Murmu, Kumar, Singh, Sahoo and Desai.)