Potential Treatment Research Articles

Esculin-Induced Apoptosis and Suppression of Leukemia Surface Markers in HL-60 and THP-1 Cells: A Potential Selective Anticancer Agent

Esculin, a natural coumarin compound primarily derived from Cortex fraxini, is known for its anti-inflammatory and antioxidant properties. Leukemia, a type of hematological cancer, is characterized by the uncontrolled proliferation of white blood cells and has high mortality rates. In this study, we aimed to investigate the potential anticancer effects of esculin (Esculetin-6-Glucoside) on leukemia cell lines, focusing on how this compound could be utilized in cancer treatment through apoptotic pathways. Our experiments used acute promyelocytic leukemia (HL-60) and acute monocytic leukemia (THP-1) cell lines. Cancer cell counting and viability analyses were conducted using the MTS assay(5-(3-carboxymethoxyphenyl)-2-(4,5-dimethylthiazol)-3-(4-sulfophenyl) tetrazolium inner salt assay). Apoptosis was assessed using FITC-labeled Annexin V and propidium iodide. Caspase-3 activation, cytochrome C release, leukemia cell surface markers, and mitochondrial membrane potential (MMP) were analyzed via flow cytometry. Our results demonstrated that esculin can induce apoptosis in leukemia cell lines. Additionally, leukemia surface markers post-treatment were statistically significantly reduced post-treatment in both cell lines. HL-60 and THP-1 cells exhibited different cellular responses in terms of MMP, Caspase-3, and Cytochrome C activities; HL-60 cells were more resistant to esculin treatment, while THP-1 cells were more sensitive. These findings suggest that esculin could become a potential agent in cancer treatment by targeting apoptotic pathways. However, more in vivo studies and preclinical modeling are needed to understand the anticancer effects of esculin fully. Evaluating its efficacy against different cancer types could further expand the therapeutic potential of this compound.

Advancing stability in inverted polymer solar cells through accelerated xenon curing of the ZnO layer

This study delves into the profound implications of employing an intensive xenon lamp treatment with a rapid curing method completed within 4 min, to fabricate a ZnO layer. Subsequently, we applied a coating of PM6:Y6 as the active layer and utilized MoO3/Ag as the contact electrode, aiming to advance the efficiency of polymer solar cells (PSCs) through entirely room-temperature processes. Our investigation juxtaposes this xenon lamp treatment with the conventional hot plate method for annealing the ZnO layer, conducted at 180 °C for both 20 min and 4 min. Remarkably, our proposed xenon lamp treatment process not only promotes charge transfer but also exhibits enhancements of the lattice oxygen in the Zn-O layer. This innovative methodology of xenon treatment yields a notable increase in power conversion efficiency (PCE), achieving 14.55 %, compared to 13.71 % and 12.44 % for the ZnO layers annealed with a hot plate for 20 min and 4 min, respectively. Moreover, devices subjected to the 4-min xenon lamp treatment maintained 85 % (T85) of their original Power Conversion Efficiency (PCE) after enduring 500 h of one-sun aging measurement. These findings evoke optimism regarding the xenon treatment's potential to streamline the fabrication process, and provide a promising avenue for mitigating interface degradation while enhancing the stability of PSCs.

Narrative review on efficacy and safety of anti-angiogenesis in combination with immunotherapy in the treatment of breast cancer.

Breast cancer was the second frequently diagnosed cancer in 2022 among all cancers. Besides classical chemotherapy and radiation, immunotherapy and targeted therapy are both identical treatment options for patients with advanced breast cancer. Immunotherapy is a therapeutic approach to control and eliminate tumors by restarting and maintaining the tumor-immunity cycle and restoring the body's normal anti-tumor immune response. Immunotherapy alone or in combination with other therapies has been shown to be clinically beneficial in a variety of solid tumors with a manageable safety profile. However, immunotherapy alone cannot fully satisfy the therapeutic needs for patients with breast cancer. Therefore, there is an urgent need for immunotherapy to be combined with other therapeutic approaches to increase treatment efficacy. We systematically searched PubMed database for relevant studies published over the past 5 years. Articles were screened for eligibility and key data extracted. We assess the current breast cancer treatment landscape, summarizing efficacy and safety of recent immunotherapy, chemotherapy combined with immunotherapy, immunotherapy combined with anti-angiogenic therapy. In the treatment of breast cancer, aiming to promote further research and applications of this novel treatment regimen in patients with breast cancer. Since anti-angiogenic therapy can reprogramme the tumor immune microenvironment, immunotherapy in combination with anti-angiogenic therapy might have a synergistic effect, igniting a new hope for immunotherapy for breast cancer patients. The review's conclusions offer insightful information on the state of breast cancer treatment today. In the end, improving clinical practice and pertinent research for immunotherapy combination therapy will contribute to bettering patient outcomes, raising quality of life, and creating more potent treatments. This review emphasizes the potential of immunotherapy combinations, especially with anti-angiogenic therapeutic regimens, as a viable strategy for the treatment of breast cancer through a thorough study of the literature. To improve treatment approaches, lessen side effects for patients, and find trustworthy biomarkers to forecast response to immunotherapy combo medicines, further research is necessary.

Neuritin alleviates Diabetic Retinopathy by Regulating Endoplasmic Reticulum Stress in Rats.

Neuritin, a small-molecule neurotrophic factor, maintains neuronal cell activity, inhibits apoptosis, promotes process growth, and regulates neural progenitor cell differentiation, migration, and synaptic maturation. Neuritin helps retinal ganglion cells (RGCs) survive optic nerve injury in rats and regenerate axons. However, the role of Neuritin in Diabetic retinopathy (DR) is unclear. This study is intended to investigate the effect and mechanism of Neuritin in DR. For this purpose, we established DR rat models and injected Neuritin into them. This study provides a potential treatment for diabetic retinopathy. The rat model of DR was established by streptozotocin (STZ) injection, and the effect of Neuritin on DR was detected by intravitreal injection. Histological analysis was performed by H&E and TUNEL methods. The mRNA and protein expressions of endoplasmic reticulum stress (ERS) pathway-related transcription factors were detected by qRT-PCR and western blot. The blood-retinal barrier (BRB) function was assessed using the patch-clamp technique and Evans blue leakage assay. Neuritin significantly improved the retinal structure, restrained the apoptosis of retinal cells, and protected the normal function of BRB in DR model rats. Mechanistically, Neuritin may function by inhibiting the expression of GRP78, ASK1, Caspase-12, VEGF, and so on. Our results indicate that Neuritin alleviates retinal damage in DR rats via the inactive endoplasmic reticulum pathway. Our study provides a potential treatment for DR.

Adipose-derived mesenchymal stromal cells: A study on safety and efficacy in ocular inflammation.

This study explores the application of adipose-derived mesenchymal stromal cells (adMSCs) as a therapy for ocular inflammatory diseases utilizing a chronic GVHD model. Human adMSCs were administered via subconjunctival injection into mice with chronic ocular GVHD. Clinical scores and changes in T cell populations were analyzed. The study showed significant improvement in corneal integrity, including epithelial damage, opacity, thickness, and structure, after subconjunctival adMSC transplantation. Additionally, adMSC transplantation increased CD45+ and Foxp3+ Tregs while decreasing CD4+ T cells, 1IL17A+ Th17cells, and IFNγ+ Th1 cells in local cervical lymph nodes. Moreover, adMSC-conditioned media enhanced wound closure and cell migration toward the wound bed in vitro. The cells disappeared within a week suggesting that trophic factors were involved. The dual benefit of adMSCs in immune-related ocular disorders underscores their potential for clinical application. This study focuses on subconjunctival delivery, effects of adMSCs and migration post-injection, with implications for optimizing cellular therapy application. The observed dual action, combining immunomodulation and tissue repair enhancement, underscores holistic approach of adMSC therapy in regenerative medicine, making it a potent treatment for diseases involving inflammation and tissue damage in the ocular surface.

QSAR Modeling, Molecular Docking and ADMET Study of Aryl Fluorosulfate Derivatives as Potential Anti-TB Agents

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, stands as a global infectious disease presenting substantial public health challenges due to its high incidence and mortality rates. The prolonged use of conventional anti-TB therapies has led to the emergence of severe drug resistance in Mtb, resulting in extended treatment durations, increased costs, poor patient compliance, and reduced cure rates. This phenomenon has posed a significant burden on global TB prevention and control efforts, necessitating a shift in research focus toward the exploration of novel anti-TB drugs. In this context, utilizing QSAR modeling methods, our study systematically investigated the relationship between the chemical structures of 36 aryl fluorosulfate derivatives and their inhibitory activity against Mtb. Robust and predictive Topomer CoMFA and HQSAR models were developed, featuring Topomer CoMFA model parameters: q 2 = 0.659, r 2 = 0.969, F = 102.877, N = 6, SEE = 0.138; HQSAR model parameters: q 2 = 0.705, r 2 = 0.873, SEE = 0.264, HL = 199, N = 4. Leveraging these models, structural modifications were applied to the compounds using the ZINC15 database, leading to the successful design and screening of three novel compounds with desirable inhibitory activity. Molecular docking and ADMET performance prediction results indicated that these three new compounds exhibit strong binding capabilities and promising pharmaceutical potential. This study provides valuable insights and research directions for the development of aryl fluorosulfate derivatives as potential agents for tuberculosis treatment and as novel drugs.

The major biogenic amine metabolites in mood disorders.

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multi-center collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders.

Modulation of Cerebellar Oscillations with Subthalamic Stimulation in Patients with Parkinson's Disease.

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson's disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations. To observe the effects of STN-DBS on cerebellar oscillations in patients with PD. We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity. In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions. While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD.

Structure-activity relationships study of N-ethylene glycol-comprising alkyl heterocyclic carboxamides against A549 lung cancer cells.

Aim: Certain cancer cells depend on oxidative phosphorylation for survival; thus, inhibiting this process may be a promising treatment strategy. This study explored the structure-activity relationships of the mitochondrial inhibitor N-ethylene glycol-comprising alkyl thiophene-3-carboxamide 3.Methods & results: We synthesized and evaluated 13 analogs (5a-m) with different ethylene glycol units, heterocyclesand connecting groups for their growth-inhibitory effects on A549 non-small cell lung cancer cells. We found that increasing the number of ethylene glycol units significantly enhanced inhibitory activity. Some analogs activated adenosine monophosphate-activated protein kinase, similar to 3. Notably, analog 5e, which contains tetraethylene glycol units, significantly inhibited tumor growth in vivo.Conclusion: Analog 5 may be a potential therapeutic agent for non-small cell lung cancer treatment.

Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Synergistic Effects of Ethanol Extract of Allium sativum (Garlic) with DAPT and ATRA on Notch Signaling Targeted Molecular Action on Lung Cancer Cell line (A549)

Background: The activated oncogenic Notch signalling is an emerging target to treat cancer progression and recurrence. Synthetic inhibitors of Notch receptors are in pre-clinical studies. However, the overexpression of Notch signalling molecules at the gene level needs to be regulated to control cancer progression. Objective: We propose that this can be achieved by gene-regulatory drugs in combination with natural phytochemical compounds. Methods: The ethanol extract of Allium sativum alone and in combination with DAPT and ATRA were evaluated for cytotoxicity on A549 cells by MTT and Trypan blue assays. Their effects on Notch 1, Hes 1 and p53 gene expressions were studied by RT-PCR and qPCR. Their inhibition on metastatic invasion of A549 cells was analyzed by in vitro wound scratch assay. The phytochemicals of the extract were identified by GC-MS analysis. Results: Many organosulfur compounds having anti-cancer potency were identified in GC-MS. The combination treatment with 50μg (IC50) of garlic extract exhibited a highly significant (P≤0.01) synergistic inhibitory effect on A549 cell growth and migration. It has also significantly reduced the expression of Notch 1 and Hes 1 oncogenes and enhanced p53 gene expression, compared with the individual treatments. This indicates the synergistic action of the extract on the downregulation of Notch signalling at the mRNA level. Conclusion: Our study results imply that the combination therapies have potent molecular treatment action via down-regulating Notch signaling target genes and upregulating p53 gene expression as an underlying mechanism of inhibitory action on A549 lung cancer cells.

Galloyl-boosted gold nanorods: Unleashing personalized cancer immunotherapy potential

Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes.

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway.

JOURNAL/nrgr/04.03/01300535-202511000-00028/figure1/v/2024-12-20T164640Z/r/image-tiff Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

Horseshoes and spiral waves: capturing the 3D flow induced by a low-mass planet analytically

ABSTRACT The key difficulty faced by 2D models for planet–disc interaction is in appropriately accounting for the impact of the disc’s vertical structure on the dynamics. 3D effects are often mimicked via softening of the planet’s potential; however, the planet-induced flow and torques often depend strongly on the choice of softening length. We show that for a linear adiabatic flow perturbing a vertically isothermal disc, there is a particular vertical average of the 3D equations of motion that exactly reproduces 2D fluid equations for arbitrary adiabatic index. There is a strong connection here with the Lubow–Pringle 2D mode of the disc. Correspondingly, we find a simple, general prescription for the consistent treatment of planetary potentials embedded within ‘2D’ discs. The flow induced by a low-mass planet involves large-scale excited spiral density waves that transport angular momentum radially away from the planet and ‘horseshoe streamlines’ within the coorbital region. We derive simple linear equations governing the flow that locally capture both effects faithfully simultaneously. We present an accurate coorbital flow solution allowing for inexpensive future study of corotation torques, and predict the vertical structure of the coorbital flow and horseshoe region width for different values of adiabatic index, as well as the vertical dependence of the initial shock location. We find strong agreement with the flow computed in 3D numerical simulations, and with 3D one-sided Lindblad torque estimates, which are a factor of 2–3 lower than values from previous 2D simulations.

Deciphering the code: the pivotal role of lncRNAs in advancing TNBC therapy.

Triple-negative breast cancer (TNBC) represents the most formidable subtype of breast cancer, characterized by a notable dearth in targeted therapeutic options. Deciphering the underlying molecular mechanisms of TNBC is pivotal for improving patient outcomes. Recent scientific advancements have spotlighted long non-coding RNAs (lncRNAs) as key players in the genesis, progression, and metastasis of cancers. This review delineates the significant influence of lncRNAs on the advancement, detection, and neoadjuvant chemotherapy efficacy in TNBC, detailing the diverse expression patterns of aberrant lncRNAs. The paper explores the specific mechanisms by which lncRNAs regulate gene expression in both the nucleus and cytoplasm, with a special focus on their involvement in TNBC's post-transcriptional landscape. Thorough investigations into TNBC-associated lncRNAs not only forge new avenues for early diagnosis and potent treatment strategies but also highlight these molecules as promising therapeutic targets, heralding an era of personalized and precision medicine in TNBC management.

A Review of the Azasteroid-type 5-alpha Reductase Inhibitors for the Management of Benign Prostatic Hyperplasia

Background: Prostate cancer is one of the most complex cancer and most common in elderly males. The prostate gland's malignant growth known as benign prostatic hyperplasia (BPH) is associated with lower urinary tract symptoms (LUTS) such as frequency hesitancy, and urgency. Various treatment strategies have been employed for management of prostate cancer. Due to its prolonged treatment, varying clinical treatment and high association with treatment related morbidity raise serious questions about the ideal treatment strategy for the patients. Except for skin cancer, prostate cancer is the most frequent cancer among men. Introduction: Prostate cancer cases were estimated at 14, 14,259 and 3, 75,304 persons were died globally in 2020. It is the fourth most frequent type of cancer to be discovered worldwide. It impacts over 75% of people by the time they turn 65 and its prevalence increases with age. It seems sensible that 5-alpha reductase inhibitors prevent the conversion of testosterone to dihydrotestosterone and would be used to treat benign prostatic hyperplasia because high levels of the 5-alpha reductase enzymes in humans lead to excessive levels of dihydrotestosterone in peripheral tissues. Methods: Finasteride (Proscar) and dutasteride (Avodart) are 5-alpha reductase inhibitors (5-ARIs) used in the treatment of lower urinary tract symptoms (LUTS) with prostatic enlargement as these suppress the androgens. Finasteride in clinical trials shows a 25% reduction in prostate cancer in randomized trials. Dutasteride (Avodart) shows the reduction in risk of prostate cancer by 23 % (approx.) but it also affects the detection of prostate cancer by affecting the levels of prostate-specific antigen. Results: The structural requirements for potential 5-alpha reductase inhibitors might be revealed via ligand-based comparative pharmacophore research employing the known strong inhibitors. These approaches can generate data can be utilized to create more effective and selective inhibitors that pharmaceutical industries can produce at a lesser price. Conclusion: 5-alpha reductase inhibitors are useful in the management of prostate cancer. However, further studies are needed to elucidate the optimal utilization, long-term effects and potential risks in prostate cancer treatment. All 5-alpha reductase inhibitor subcategories have been addressed in this review.

Latest Delivery Advancements of Lipid Nanoparticles for Cancer Treatment.

As one of the primary causes of illness and death globally, cancer demands novel and potent treatment approaches, which is why lipid nanoparticles (LNPs) have gained attention as a promising delivery system for anticancer drugs with precision and efficacy. The article discusses the salient characteristics of LNPs, such as the lipid components, particle size, polydispersity index, and encapsulation efficiency, followed by strategies that enhance their remarkable drug delivery capabilities. The articles explore LNPs ability to improve the solubility, stability, and bioavailability of various chemotherapeutics, nucleic acids, and immunotherapeutic modalities. It also highlights the recent advancement in surface modification of LNPs, which is essential to improve their effectiveness. Tailored coatings of LNPs improve targeting precision, stability, and biocompatibility; enhancing their transport to boost therapeutic efficacy for cancer targeting. The review summarizes the recent advancements made in using LNPs to treat different forms of cancer and focuses on the most recent clinical studies. Overall, the review highlights that the LNPs can target and treat cancer in a tailored manner through gene therapy, RNA interference, and immunotherapy.

Callus of Mundulea sericea as potential anti-diabetic agents; an in silico approach

Mundulea sericea, a rare plant of the fabaceae family, has high medicinal value but a low regeneration rate in its natural habitat. The present study aims to conduct in vitro propagation and screen the potential bioactive compounds in the callus through in silico analysis. The explants were collected, sterilized, and inoculated in a standardized MS media with growth regulators in vitro to obtain sterile plants. The experiment resulted in the formation of a greenish-brown callus at a rate of 82.41 % on MS medium supplemented with BAP (6.66 µM L−1). The callus was powdered and subjected to GC–MS analysis. A total of 31 compounds were identified in the methanolic extract, along with their corresponding peak values. The compounds underwent ADME analysis for toxicity predictions. Eight compounds were chosen further based on pharmacokinetic and pharmacodynamic properties. The selected ligands were docked with anti-diabetic targets α-amylase and α-glucosidase. As a result, the compound CID 5283663 exhibited a strong binding affinity of −9.3 with the α-amylase receptor. The ligand CID 33010 exhibits a strong interaction of −7.5 with the α-glucosidase receptor. Glibenclamide and acarbose were used as standards. This study is the first attempt to identify compounds in the callus extract that could inhibit α-amylase and α-glucosidase enzymes. The findings from molecular docking analysis suggest these compounds could become potent treatments for diabetics, showcasing the promise of natural sources in drug discovery.

Integrating Computational Design and Experimental Approaches for Next-Generation Biologics.

Therapeutic protein engineering has revolutionized medicine by enabling the development of highly specific and potent treatments for a wide range of diseases. This review examines recent advances in computational and experimental approaches for engineering improved protein therapeutics. Key areas of focus include antibody engineering, enzyme replacement therapies, and cytokine-based drugs. Computational methods like structure-based design, machine learning integration, and protein language models have dramatically enhanced our ability to predict protein properties and guide engineering efforts. Experimental techniques such as directed evolution and rational design approaches continue to evolve, with high-throughput methods accelerating the discovery process. Applications of these methods have led to breakthroughs in affinity maturation, bispecific antibodies, enzyme stability enhancement, and the development of conditionally active cytokines. Emerging approaches like intracellular protein delivery, stimulus-responsive proteins, and de novo designed therapeutic proteins offer exciting new possibilities. However, challenges remain in predicting in vivo behavior, scalable manufacturing, immunogenicity mitigation, and targeted delivery. Addressing these challenges will require continued integration of computational and experimental methods, as well as a deeper understanding of protein behavior in complex physiological environments. As the field advances, we can anticipate increasingly sophisticated and effective protein therapeutics for treating human diseases.

Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo-Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury.

In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen-treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation-targeting prowess while sidestepping the release of pro-inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid-loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy "Trojan horse" in the battle against pneumonia-induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.