Curative Potential Research Articles

Awareness And Current Knowledge Of Medicinal Plants

Abstract Objectives This research attempts to investigate the historical applications of plants for therapeutic reasons, follow the development of these applications, and comprehend the influence of artificial methods on the use of medicinal plants. Methods The study involves the examination of antique writings from Mesopotamia, Egypt, Greece, and the Islamic world, as well as a 5,000-year-old Sumerian clay tablet discovered in Nagpur. The study examined historical reports of a number of therapeutic plants, including Glycyrrhiza glabra, Cupressus sempervirens, Commiphora myrrha, Cedrus duham, and Papaver somniferum. It also looked at how improved methods of separating active plant components were developed in the early 19th century, as opposed to more crude treatments like tinctures and powders. Key Findings Historical evidence reveals that ancient cultures used a wide variety of plants for medicinal reasons, preparing them in different ways. The development of synthetic methods in the 19th century completely changed the manufacture of pharmaceuticals by making it possible to replicate active ingredients precisely and in large quantities. With more than 250,000 plant species recognized, nature's wide diversity of plant metabolites highlights the importance of plants in both traditional and contemporary medicine. Conclusions The development of contemporary synthetic approaches from traditional plant-based medicines serves as an example of how far medicine has come. While modern techniques have increased the effectiveness and scalability of medicinal manufacturing, the historical usage of plants demonstrates a profound grasp of their curative potential. The vast diversity of plant metabolites continues to be important for health and medicine despite advancements in synthetic approaches, highlighting the ongoing importance of natural resources in pharmaceutical research.

Controlled release of hydrogel-encapsulated mesenchymal stem cells-conditioned medium promotes functional liver regeneration after hepatectomy in metabolic dysfunction-associated steatotic liver disease

BackgroundGlobally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis.MethodsMale Lewis rats were fed with a methionine and choline–deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV).ResultsThe regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division.ConclusionsMSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx.

Insight to Biofabrication of Liver Microtissues for Disease Modeling: Challenges and Opportunities.

In the last decade, liver diseases with high mortality rates have become one of the most important health problems in the world. Organ transplantation is currently considered the most effective treatment for compensatory liver failure. An increasing number of patients and shortage of donors has led to the attention of reconstructive medicine methods researchers. The biggest challenge in the development of drugs effective in chronic liver disease is the lack of a suitable preclinical model that can mimic the microenvironment of liver problems. Organoid technology is a rapidly evolving field that enables researchers to reconstruct, evaluate, and manipulate intricate biological processes in vitro. These systems provide a biomimetic model for studying the intercellular interactions necessary for proper organ function and architecture in vivo. Liver organoids, formed by the self-assembly of hepatocytes, are microtissues and can exhibit specific liver characteristics for a long time in vitro. Hepatic organoids are identified as an impressive tool for evaluating potential cures and modeling liver diseases. Modeling various liver diseases, including tumors, fibrosis, non-alcoholic fatty liver, etc., allows the study of the effects of various drugs on these diseases in personalized medicine. Here, we summarize the literature relating to the hepatic stem cell microenvironment and the formation of liver Organoids.

Hematopoietic Cell Transplant compared with Standard Care in Adolescents and Young Adults with Sickle Cell Disease

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation. The primary endpoint was the comparison of survival 2 years after biologic assignment between treatment arms. Power calculations required 60 participants on the Donor Arm and 140 on the No Donor Arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives compared changes in SCD-related events, functional outcomes, and organ function. Data were analyzed by the intent-to-treat principle. A total of 113 participants were enrolled, 28 on the Donor and 85 on the No Donor Arm The 2-year probabilities of survival were 89% and 93%, on the Donor and No Donor Arms, respectively. Vaso-occlusive pain (VOC) was less frequent on the Donor Arm in the second year after biologic assignment (p < 0.001). On PROMIS-57 surveys there was decreased fatigue (p=0.003) and an increased ability to participate in social roles and activities (p=0.003) on the Donor Arm 2-years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the Donor Arm led to improvements in VOC, fatigue, and social function.

Therapy concepts in type 1 diabetes mellitus treatment: disease modifying versus curative approaches.

For many autoimmune diseases, including type 1 diabetes mellitus (T1DM), efforts have been made to modify the disease process through pharmacotherapy. The ultimate goal must be to develop therapies with curative potential by achieving an organ without signs of parenchymal cell destruction and without signs of immune cell infiltration. In the case of the pancreas, this means regenerated and well-preserved beta cells in the islets without activated infiltrating immune cells. Recent research has opened up the prospect of successful antibody combination therapy for autoimmune diabetes with curative potential. This goal cannot be achieved with monotherapies. The requirements for the implementation of such a therapy with curative potential for the benefit of patients with T1DM and LADA (latent autoimmune diabetes in adults) are considered.

Revolutionizing Cardiac Care: The Role of Gene Therapy in Treating Cardiomyopathy

Gene therapy presents a method for addressing types of cardiomyopathies that play a substantial role in heart failure. This innovative approach, leveraging technologies such as clustered regularly interspaced short palindromic repeats/Cas9 for modifying genomes, holds promise for lasting treatments or potential cures that go beyond therapies. It is essential to grasp the workings of gene therapy, including gene silencing, clustered regularly interspaced short palindromic repeats genome editing, and enhancing sarcomere function to effectively apply it to treating cardiomyopathy. Examining current trials will shed light on the advancements and accomplishments in this field while also addressing the obstacles, uncertainties, and opportunities ahead. Delving into the possibilities of gene therapy involves exploring targets and inventive delivery methods that underscore the evolving landscape of research in this domain hinting at a future brimming with opportunities to transform care. The progress made in using gene therapy to treat cardiomyopathies represents the progress of medicine in driving forward scientific innovation to provide more precise and enduring solutions for patients. Continuously refining gene therapy techniques and deepening our knowledge of genetics are factors that will shape the future direction of cardiac care. The potential of gene therapy does not just benefit individuals with cardiomyopathy but also represents a move toward effective treatments for various genetic conditions. This signifies a step in the pursuit of holistic healthcare solutions.

Molecular interactions of plant-derived inhibitors from Euphorbia hirta against binding sites of HPV E6 and E7 oncoproteins - An in-silico analysis

Although no cure for Human Papilloma virus (HPV) exists at the moment, effective vaccines are present that can prevent the most harmful strains of the virus from infecting people. While potential cures like therapeutic vaccines, immunotherapy, and gene therapy are still in the early stages of development and may take years to become widely available, we focussed on using traditional Siddha-based medicines (phytochemicals of Euphorbia hirta L.) as a prospect through in-silico docking studies. Twelve phytochemicals from Euphorbia hirta L. were selected to investigate the antiviral properties against HPV. These ligand structures were obtained from PubChem database, prepared for docking with two major HPV targets i.e., E6 and E7 oncoproteins obtained from PDB, using AutoDock tools. The analysis revealed the potential of lobeline and euphol ligands effectively binding to the active sites of E6 and E7 proteins respectively. Using the ADMET lab 2.0 server, the ligands were evaluated for their commercial drug potential by considering their absorption, distribution, metabolism, excretion, and toxicity properties.

Synthesis and antifungal activity of novel piperidinyl thiazole derivatives.

As an investigative program around the development of novel oomycetes fungicides, a systematic exploration of piperidinyl thiazole fungicides employing a bioisosteric replacement strategy was planned. A series of novel piperidinyl thiazole analogues were designed, synthesised, and evaluated as fungicides in vitro and in vivo against three oomycete fungal pathogens: Phytophthora infestans (P. infestans), Plasmopara viticola (P. viticola), and Pseudoperonospora cubensis (P. cubensis). Variation at four different regions of piperidinyl thiazole fungicides like Oxathiapiprolin and Fluoxapiprolin was considered. All variations delivered excellent in vitro and in vivo activity against P. infestans at extremely low concentrations. O-linked heterocyles, bicyclic piperidines, and sulfoximine-substituted aryls demonstrated the most robust transfer of in vitro activity into the greenhouse, while pyridones, acylated sulfoximines, and sultams showed less consistent results concerning the transfer. Specific compounds were selected for deeper evaluation of oomycetes activity. Several of them with representatives of all the series showed an excellent in vivo activity against P. viticola and P. cubensis. Among the most active compounds, P14 and P25 were further profiled in advanced studies and were found to have a robust curative potential. P14, P15, and P25 provided excellent control of P. infestans (in potato), P. viticola (in grapes), and P. cubensis (in cucumber) in field trials at dose rates of 20 and 30 g per hectare. A bioisosteric replacement strategy was successfully employed to identify novel piperidine thiazole derivatives with robust and commercially interesting control of oomycetes diseases in the greenhouse and under field conditions. A systematic exploration of various modifications of the piperidine thiazole class and their structure activity relationships was described. © 2024 Society of Chemical Industry.

Hepatitis B

Hepatitis B is a viral infection caused by the Hepatitis B virus (HBV), primarily affecting the liver and leading to both acute and chronic disease. With over 250 million individuals suffering from chronic Hepatitis B, it poses a significant global health challenge, being a leading cause of liver cirrhosis, liver failure, and hepatocellular carcinoma. This study aims to elucidate the transmission pathways, treatment options, and necessary public health strategies for Hepatitis B. We analyze the modes of transmission, which include contact with infectious body fluids—primarily through perinatal transmission, unprotected sexual contact, and sharing contaminated needles. Despite the availability of an effective vaccine since the 1980s, Hepatitis B remains endemic in many parts of Asia and Africa due to limited immunization coverage. The pathogenesis of HBV involves complex interactions between the virus and the host immune system, potentially leading to liver inflammation and fibrosis. Clinical presentations vary widely, ranging from asymptomatic infections to severe liver disease. Current treatment options for chronic Hepatitis B include antiviral medications such as tenofovir and entecavir, which suppress viral replication but do not cure the infection. Recent advancements in therapeutic strategies, including novel antivirals and immune modulators, show promise for more effective management and potential cures in the future. Comprehensive public health strategies—such as vaccination, screening, and education—are crucial for controlling the spread of HBV and reducing the global burden of Hepatitis B-related complications.

Spinocerebellar ataxia type 7: A case report

Introduction: Spinocerebellar ataxia type 7 is part of a rare group of neurodegenerative diseases, characterized by lesions in the brainstem, cerebellum, spinal cord, and retina, manifesting as motor disturbances associated with signs of pyramidal involvement and amaurosis. The dysfunction is caused by autosomal dominant genetic alterations, with disease severity and the age of symptom onset being directly linked to the patient’s genetic expression. Case Report: We present the case of a 24-year-old woman, previously healthy, who denied smoking, drinking alcohol, or taking any other drugs. She reported that approximately nine months, she had experienced a decline in dexterity for tasks requiring fine motor skills. She also exhibited impaired gait, frequent falls, and difficulties in performing basic activities of daily living (ADLs). On neurological examination, she presented with an ataxic and staggering gait, tremor during movement, dysmetria, dysdiadochokinesia, movement decomposition, dysarthria (scanning speech), dysphagia, dystasia, dysbasia, and nystagmus, all of which are indicative of cerebellar impairment. A genetic panel revealed the presence of 44 cytosine-adenine-guanine nucleotide repeat expansions on allele 2 of the ATXN7 gene, confirming the diagnosis of spinocerebellar ataxia type 7. Conclusion: In this case report, the diagnosis of spinocerebellar ataxia was established through a comprehensive assessment of the patient’s clinical history, neurological examination, imaging studies, and genetic profiling, all of which are essential for reaching a definitive diagnosis. The prognosis for this disease varies due to ongoing research into its pathophysiology. Furthermore, discussions within the scientific community regarding potential cures for this condition continue

Optimizing cryopreservation strategies for scalable cell therapies: A comprehensive review with insights from iPSC-derived therapies.

Off-the-shelf cell therapies hold significant curative potential for conditions, such as Parkinson's disease and heart failure. However, these therapies face unique cryopreservation challenges, especially when novel routes of administration, such as intracerebral or epicardial injection, require cryopreservation media that are safe for direct post-thaw administration. Current practices often involve post-thaw washing to remove dimethyl sulfoxide (Me2SO), a cytotoxic cryoprotective agent, which complicates the development and clinical translation of off-the-shelf therapies. To overcome these obstacles, there is a critical need to explore Me2SO-free cryopreservation methods. While such methods typically yield suboptimal post-thaw viability with conventional slow-freeze protocols, optimizing freezing profiles offers a promising strategy to enhance their performance. This comprehensive review examines the latest advancements in cryopreservation techniques across various cell therapy platforms, with a specific case study of iPSC-derived therapies used to illustrate the scalability challenges. By identifying key thermodynamic and biochemical phenomena that occur during freezing, this review aims to identify cell-type independent approaches to improve the efficiency and efficacy of cryopreservation strategies, thereby supporting the widespread adoption and clinical success of off-the-shelf cell therapies.

Comparative efficacy of different exercise modalities on metabolic profiles and liver functions in non-alcoholic fatty liver disease: a network meta-analysis.

Research evidence suggests that exercise is a potent therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Many investigations have delved into the curative potential of diverse exercise regimens on NAFLD. This investigation synthesizes findings from randomized controlled trials via a network meta-analysis to evaluate the efficacy of exercise-based interventions on NAFLD. We conducted a search across five electronic databases (Web of Science, EMBASE, PubMed, SCOPUS, and CNKI)to identify randomized controlled trials (RCTs) comparing the effects of different exercise modalities on metabolic profiles and liver functions in patients with NAFLD. The literature search was comprehensive up to 15, December 2023. The selected studies were subjected to a rigorous quality appraisal and risk of bias analysis in accordance with the Cochrane Handbook's guidelines, version 5.1.0. We employed Stata/MP 17 for the network meta-analysis, presenting effect sizes as standardized mean differences (SMD). This study aggregated results from 28 studies, involving a total of 1,606 participants. The network meta-analysis revealed that aerobic exercise was the most effective intervention for improving BMI in patients with NAFLD, demonstrating a significant decrease in BMI (-0.72, 95%CI: -0.98 to -0.46; p < 0.05; Surface Under the Cumulative Ranking (SUCRA) = 79.8%). HIIT was the top intervention for enhancing HDL-C (0.12, 95% CI: 0.04 to 0.20; p < 0.05; SUCRA = 76.1%). Resistance exercise was the most effective for reducing LDL-C (-0.20, 95% CI: -0.33 to -0.06; p < 0.05; SUCRA = 69.7%). Mind-body exercise showed superior effectiveness in improving TC (-0.67, 95% CI: -1.10 to -0.24; p < 0.05; SUCRA = 89.7%), TG = -0.67, 95% CI: -1.10 to -0.24; p < 0.05; SUCRA = 99.6%), AST (-8.07, 95% CI: -12.88 to -3.25; p < 0.05; SUCRA = 76.1%), ALT (-12.56, 95% CI: -17.54 to -7.58; p < 0.05; SUCRA = 99.5%), and GGT (-13.77, 95% CI: -22.00 to -5.54; p < 0.05; SUCRA = 81.8%). This network meta-analysis demonstrates that exercise interventions positively affect various metabolic profiles and liver functions in NAFLD patients. Mind-body exercises are particularly effective, surpassing other exercise forms in improving metabolic profiles and liver functions. https://www.crd.york.ac.uk/PROSPERO/, identifier registration number CRD42024526332.

Unwrapping the immunological alterations in testicular germ cell tumors: From immune homeostasis to malignancy and emerging immunotherapies.

Testicular germ cell tumors (TGCTs), derived from primordial germ cells, are rare malignancies with high curative potential. However, the emergence of new evidence indicating that 15% of patients experience tumor progression, leading to death, underscores the need for innovative therapeutics. This review aimed to explore the immune status in maintaining testicular health and the immune-related aspects of malignancy. Furthermore, it presents an overview of current data on the use of immunotherapy for TGCT patients. Recent advances in immunology have opened a promising avenue for studying diseases and highlighted its role in treating diseases. While the immunopathological facets of TGCTs are not fully understood, investigations suggest a complex interplay among testis-resident immune cells, testis-specific cells (i.e., Sertoli cells (SCs) and Leydig cells (LCs)), and immune-regulating mediators (e.g., sex hormones) in the normal testicle that foster the testicular immune privilege (TIP). Although TIP plays a crucial role in sperm production, it also makes testis vulnerable to tumor development. In the context of cancer-related inflammation, disruption of TIP leads to an imbalanced immune response, resulting in chronic inflammation that can contribute to testicular tissue dysfunction or loss, potentially aiding in cancer invasion and progression. Comparing the immune profiles of normal and malignant testes is valuable and may provide insights into different aspects of testicular immunity and immune-based treatment approaches. For patients resistant to chemotherapy and with a poor prognosis, immunotherapy has shown promising results. However, its effectiveness in treating resistant TGCTs or preventing tumor recurrence is still uncertain.

Human Immune System, Its Levels, and Disorders in the Context of HIV/AIDS: A Comprehensive Review

The human immune system is a complex and multi-tiered defense mechanism that safeguards the body from infections and diseases. This comprehensive review explores the structure and function of the immune system, detailing its two primary components: innate and adaptive immunity. While innate immunity offers immediate, nonspecific defense, adaptive immunity provides long-term protection by targeting specific pathogens. The review delves into the impact of HIV on the immune system, focusing on how the virus specifically targets and depletes CD4+ T cells, leading to immune system dysregulation and the progression to AIDS. The discussion includes the stages of HIV infection, the virus’s mechanisms of immune evasion, and the resulting immune dysfunctions such as immunodeficiency, chronic inflammation, and autoimmune disorders. Opportunistic infections like tuberculosis and hepatitis are also examined in the context of HIV-induced immune suppression. Advances in HIV/AIDS treatment, particularly the role of antiretroviral therapy (ART), are highlighted, emphasizing ART’s effectiveness in preserving immune function and improving patient outcomes. The review concludes by addressing ongoing challenges with ART adherence, access to treatment, and drug resistance, while also exploring emerging research into potential cures, including gene therapy and therapeutic vaccines. Through a detailed exploration of the human immune system and its vulnerabilities to HIV, this review underscores the importance of continued research and intervention in combating the global HIV/AIDS epidemic. Keywords: Human immune system, HIV/AIDS, CD4+ T cells, innate immunity, adaptive immunity, immunodeficiency

Innovations in HIV Prevention and Treatment: The Future of HIV Care

The Human Immunodeficiency Virus (HIV) continues to pose a significant global health challenge, despite substantial progress in treatment and prevention. This review explored recent innovations in HIV prevention and treatment, highlighting advancements such as long-acting pre-exposure prophylaxis (PrEP), long-acting injectable antiretroviral therapy (ART), and emerging research into potential cures. It also examined integrated care approaches, digital health innovations, and innovative financing models that are shaping the future of HIV care. The review synthesized recent research, evaluated the impact of these innovations, and discussed future directions to advance global health goals. The methodology for this review involved a comprehensive analysis of current literature, clinical trial data, and expert opinions to provide a holistic overview of how these advancements are transforming HIV care and addressing existing challenges. Keywords: HIV Innovations, Prevention Strategies, Long-Acting ART, Integrated Care Models, Digital Health Technologies.

Investigation into the curative potential of dietary vitamin c supplementation on atrazine toxicity: behaviour and growth performance of &lt;i&gt;Clarias gariepinus&lt;/i&gt; Juveniles (Burchell, 1822)

Investigation into the curative potential of dietary vitamin c supplementation on atrazine toxicity: behaviour and growth performance of &lt;i&gt;Clarias gariepinus&lt;/i&gt; Juveniles (Burchell, 1822)

Uncovering the pharmacological mechanisms of Patchouli essential oil for treating ulcerative colitis

Ethnopharmacological relevancePogostemonis Herba has long been used in traditional Chinese medicine to treat inflammatory disorders. Patchouli essential oil (PEO) is the primary component of Pogostemonis Herba, and it has been suggested to offer curative potential when applied to treat ulcerative colitis (UC). However, the pharmacological mechanisms of PEO for treating UC remain to be clarified. Aim of the studyTo elucidate the pharmacological mechanisms of PEO for treating UC. Methods and resultsIn the present study, transcriptomic and network pharmacology approaches were combined to clarify the mechanisms of PEO for treating UC. Our results reveal that rectal PEO administration in UC model mice significantly alleviated symptoms of UC. In addition, PEO effectively suppressed colonic inflammation and oxidative stress. Mechanistically, PEO can ameliorate UC mice by modulating gut microbiota, inhibiting inflammatory targets (OPTC, PTN, IFIT3, EGFR, and TLR4), and inhibiting the PI3K-AKT pathway. Next, the 11 potential bioactive components that play a role in PEO's anti-UC mechanism were identified, and the therapeutic efficacy of the pogostone (a bioactive component) in UC mice was partially validated. ConclusionThis study highlights the mechanisms through which PEO can treat UC, providing a rigorous scientific foundation for future efforts to develop and apply PEO for treating UC.

Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol-induced nephrotoxicity.

Tramadol (TR), a commonly prescribed pain reliever for moderate to severe pain, has been associated with kidney damage. This study investigates TR-induced nephrotoxicity mechanisms, focusing on its effects on renal proximal tubular cells (PTCs). The study findings demonstrate that TR disrupts PTC bioenergetic processes, leading to oxidative stress and inflammation. Significant toxicity to PTCs was observed with estimated effective concentration 50 values of 9.8 and 11.5 µM based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. TR also interferes with the function of PTC transporters, including organic cation uptake transporter 1, organic cation transporter 2, P-glycoprotein, and multidrug resistance protein 2. Furthermore, bioenergetics assays showed that TR reduced the activities of mitochondrial complexes I and III, adenosine triphosphate production, mitochondrial membrane potential, and oxygen consumption rate while increasing lactate release. TR also increased the production of reactive oxygen species, lipid peroxidation thiobarbituric acid reactive substances end products, and the expression of the NRf2 gene while decreasing reduced glutathione (GSH-R) stores and catalase and superoxide dismutase antioxidant activities. Additionally, TR increased the production of inflammatory cytokines (TNF-α and IL-6) and their coding genes expression. Interestingly, the study found that antioxidants like GSH-R, inhibitors of IL-6 and TNF-α, and mitochondrial activating Co-Q10 could protect cells against TR-induced cytotoxicity. The study suggests that TR causes nephrotoxicity by disrupting bioenergetic processes, causing oxidative stress and inflammation, but antioxidants and agents targeting mitochondria may have protective and curative potential.

Potential role of B- and NK-cells in the pathogenesis of pediatric aplastic anemia through deep phenotyping.

Pediatric patients with unexplained bone marrow failure (BMF) are often categorized as aplastic anemia (AA). Based on the accepted hypothesis of an auto-immune mechanism underlying AA, immune suppressive therapy (IST) might be effective. However, due to the lack of diagnostic tools to identify immune AA and prognostic markers to predict IST response together with the unequaled curative potential of hematopoietic stem cell transplantation (HSCT), most pediatric severe AA patients are momentarily treated by HSCT if available. Although several studies indicate oligoclonal T-cells with cytotoxic activities towards the hematopoietic stem cells, increasing evidence points towards defective inhibitory mechanisms failing to inhibit auto-reactive T-cells. We aimed to investigate the role of NK- and B-cells in seven pediatric AA patients through a comprehensive analysis of paired bone marrow and peripheral blood samples with spectral flow cytometry in comparison to healthy age-matched bone marrow donors. We observed a reduced absolute number of NK-cells in peripheral blood of AA patients with a skewed distribution towards CD56bright NK-cells in a subgroup of patients. The enriched CD56bright NK-cells had a lower expression of CD45RA and TIGIT and a higher expression of CD16, compared to healthy donors. Functional analysis revealed no differences in degranulation. However, IFN-γ production and perforin expression of NK-cells were reduced in the CD56bright-enriched patient group. The diminished NK-cell function in this subgroup might underly the auto-immunity. Importantly, NK-function of AA patients with reduced CD56bright NK-cells was comparable to healthy donors. Also, B-cell counts were lower in AA patients. Subset analysis revealed a trend towards reduction of transitional B-cells in both absolute and relative numbers compared to healthy controls. As these cells were previously hypothesized as regulatory cells in AA, decreased numbers might be involved in defective inhibition of auto-reactive T-cells. Interestingly, even in patients with normal distribution of precursor B-cells, the transitional compartment was reduced, indicating partial differentiation failure from immature to transitional B-cells or a selective loss. Our findings provide a base for future studies to unravel the role of transitional B-cells and CD56bright NK-cells in larger cohorts of pediatric AA patients as diagnostic markers for immune AA and targets for therapeutic interventions.

Two-year Outcomes of Ultra-low-dose Radiotherapy in the Treatment of Ocular Adnexal B-cell Lymphomas.

This study focuses on the efficacy and 2-year outcomes of ultra-low-dose radiotherapy (RT) in treating primary and secondary ocular adnexal lymphoma (OAL). A retrospective analysis was conducted on patients with OAL between 2017 and 2022, treated with 4 Gy of RT. The primary and secondary outcomes assessed were response rate, progression-free survival, and lymphoma-related death. Twenty-one patients with primary and secondary OAL of diverse, presentations, subtypes, and stages were included. The orbital tumors had an average size of 17 × 16 × 16 mm. Of the 14 primary OAL cases, 3 (14%) had T1N0M0 disease, 8 (38%) T2N0M0, and 3 (14%) T3N0M0 (AJCC 8th edition staging); of the 7 secondary OALs, 4 (19%) were stage IE, 2 (10%) stage IIE, and 1 (5%) stage IIIE (Ann Arbor staging). Ultra-low-dose RT yielded a 95% complete response rate and 100% progression-free survival rates, both locally and systemically at 2 years. Mild dry eyes were reported in 14% of patients as a late treatment toxicity. Ultra-low-dose RT emerges as an effective and well-tolerated treatment approach for OAL. Our findings support the use of 4 Gy, showcasing high complete response rates (95%) and durable disease control without significant local relapses over an average follow up of 27 months. Our results align with earlier investigations, validating the curative potential of ultra-low-dose RT and reinforcing the concept of achieving favorable outcomes with minimal intervention. This approach may potentially alleviate the burden of long-term ocular side effects associated with higher radiation doses, enhancing the overall quality of life for OAL patients.