Abstract Background Chemokine receptor type 5 (CCR5) is expressed on hepatic stellate cells (HSCs), which, together with fibroblasts, are major producers of extracellular matrix during liver fibrosis. Leronlimab is a humanized IgG4κ monoclonal antibody that binds to CCR5. The objective of the present study was to evaluate the antifibrotic effects of leronlimab in three independent preclinical studies using two mouse models of liver fibrosis. Methods In STAM™ (Stelic Animal Model) model 1, leronlimab was administered at doses of 5 or 10 mg/kg/week for 3 weeks. STAM model 2 was conducted as a confirmatory study to validate the antifibrotic effect observed with the 10 mg/kg/week dose in STAM model 1. In a third study, a carbon tetrachloride (CCl₄)-induced liver fibrosis mouse model was used to evaluate leronlimab administered at 10 mg/kg/week for 3 weeks. An isotype-matched control antibody was included in all studies for comparison. Evaluations included liver enzymes and histological assessment of liver fibrosis. Results In STAM model 1, leronlimab at 10 mg/kg/week significantly reduced fibrosis area compared with the isotype control (p = 0.0005). These findings were confirmed in STAM model 2 (p < 0.0001). Consistent antifibrotic effects were also observed in the CCl₄-induced liver fibrosis model (p = 0.0006). Conclusions Collectively, these preclinical results demonstrate that CCR5 blockade by leronlimab is associated with a significant reduction of established liver fibrosis in multiple mouse models and support further evaluation of leronlimab as a potential therapeutic option, either as monotherapy or in combination regimens, for chronic liver diseases with fibrosis.
Transfusions of fresh blood products are a vital part of modern medical care, but they still carry the risk of transmitting infections. To address this, Pathogen Reduction Technologies (PRTs) have been developed as an added safety layer by deactivating potential infectious agents in blood components. This systematic review and meta-analysis, conducted in line with PRISMA guidelines, examined how effectively these technologies improve transfusion safety and public health. A thorough search of PubMed, Scopus, and Google Scholar identified peer- reviewed, full-text studies published in English over the last decade. Eligible studies compared pathogen-reduced blood products with standard ones. Data on Transfusion-Transmitted Infections (TTIs) and Transfusion-Related Adverse Events (TRAEs) were extracted and analysed using a random-effects model in RevMan 5.4, with pooled Odds Ratios (ORs) and 95% Confidence Intervals (CIs). Six studies were included, covering more than five million platelet transfusions. All focused on the INTERCEPT® system, which uses amotosalen and UVA light. The meta- analysis found a significantly lower risk of TTIs in PRT-treated platelets (OR 14.42; 95% CI 3.57-58.18; P=0.0002; I²=29%). While the overall rate of TRAEs was not significantly different (OR 1.13; 95% CI 0.80-1.60; P=0.49), subgroup analysis showed notable reductions in Allergic Reactions (ATRs), Severe Adverse Reactions (SARs), Transfusion-Associated Circulatory Overload (TACO), and Transfusion-Related Acute Lung Injury (TRALI). These findings suggest that PRTs-particularly the INTERCEPT® system-effectively reduce transfusion-related infection risks without compromising overall safety. Keywords PRT treated platelet concentrates; Transfusion-transmitted infections; Intercept system; TACO; TRALI; SARs; TRAEs.
TIntraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas was first reported from Japan 45 years ago [1, 2]. It was called “mucin-producing tumors of the pancreas” at that time. Although it has also been called by many names other than this, it has undergone historical changes and has now been standardized to IPMT [3] and then the current term IPMN [4]. The most interesting and striking feature of IPMN is “dual carcinogenesis” in the pancreas with IPMN [5]. First, IPMN itself can progress from benign hyperplasia to low- grade dysplasia, then to high-grade dysplasia and finally to invasive carcinoma. Second, conventional pancreatic cancer may occur at a higher-than-normal rate anywhere in the pancreas other than IPMN [6,7]. Although many retrospective statistical studies have been reported on this dual carcinogenesis [8,9], the actual incidence of cancer remains to be clarified.
Salvia sclarea (clary sage) is an essential oil known for its calming and pain relieving properties. In the past, it was used to treat depression in menopausal women. However, it can also be used in terms of relaxing one’s body, relieving menstrual cramp, alleviating hot flashes, and boosting immunity. With so many clinical applications, this paper explains how this essential oil brings additional benefits through thermoregulation and patency together which can shed light in bringing the therapeutics of this essential oil to a safer but also more effective applications. In this paper, a blend was introduced to treat hot flashes due to hypertension and menopause, the rationale will be discussed. Moreover, the depth of the penetration against the effectiveness will be studied to yield a more complete and thorough results that will give a more precise picture on what elements should be included in doing a thermoregulated study. This study also points out that replenishment is a very important element in an anti-inflammation treatment plan. Without it, the desired results may not be able to achieve.
Brain-Derived Neurotrophic Factor (BDNF) is a polypeptide with a pivotal role in maintaining neuroplasticity (intended as the brain’s ability to modify its connections and functionality in response to experiences and learning) [1]. BDNF mainly promotes the survival, growth, and differentiation of both neurons and synapsis. BDNF shows neuroprotective effects, potentially preserving neurons from damage and degeneration. BDNF is implicated in mood regulation, and its dysregulation has been linked to depression and other mood disorders [2]. BDNF is also involved in the regulation of inflammatory response directly (via down-regulation of NF-kB [3] and, therefore, of the main steroid mediators of inflammation) and indirectly (via up-regulation of IL-10) [4], and in ROS modulation increasing the expression of genes encoding for scavenger enzyme systems such as Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) [5,6].
Background: Iron Deficiency Anaemia (IDA) is a major health concern in India. Livogen®Z (manufactured by Procter and Gamble Health Ltd.) combines ferrous fumarate (152mg), folic acid (750mcg) and zinc sulphate (61.8mg) for management of anaemia, but real-world data from India is scarce. Methods: A phase IV, prospective observational study was conducted at four sites in India in pregnant and non pregnant women with IDA aged 18-55 years. Subjects received Livogen®Z tablet twice daily for 90 days between June 2022 and October-2023. The primary objective was to evaluate the Change from Baseline (CFB) in Hemoglobin (Hb) after 90 days of treatment. CFB at Days 21 and 60, CFB in ferritin at end-of-study. IDA symptoms and Adverse Events (AE) were secondary endpoints. Results: Of the 102 recruited subjects, data for 69 women were included (62.3% nonpregnant, 11.6% first trimester, 26.1% second trimester) in the final analysis after excluding data for 33 subjects at one site that was non-compliant with good clinical practices. At Day 90, the mean Hb CFB was 2.2 g/dL (p<0.0001). Mean Hb CFB was 1.1 g/ dL (p<0.0001) on Day 21 and 1.9 g/dL (p<0.0001) on Day 60. At Day 90, median ferritin CFB was 12.0 ng/mL (p<0.0001) and 29.5% of women were symptom-free vs. 2.9% at study start. The treatment was well tolerated with no AEs reported by 49.3% of subjects and no serious AEs reported. Conclusion: Livogen®Z improves iron status, alleviates symptoms in women with IDA and is well-tolerated. Clinically significant improvements in Hb and ferritin levels with accompanying meaningful symptom benefits with relatively few AEs highlight Livogen®Z treatment as a favorable IDA management option.
Rice bran, a by-product of the rice milling process, is often discarded as a wasted resource despite its high nutritional value. This study focused on the fermentation process and mixing of rice bran with other agricultural wastes to make effective use of rice bran as fish feed, and aimed to clarify the effects of feeds prepared by adding sunflower meal and soybean meal to rice bran and fermented rice bran on growth and proximate composition. In the experiment, Japanese rice bran was fermented with Bacillus subtilis natto and lactic acid bacteria to produce Unfermented Rice bran Feed (URF) and Fermented Rice bran Feed (FRF), which were compared with Commercial Feed (COF). Fermentation increased the crude protein content of rice bran and decreased the crude fat content; the results of a 28-day rearing trial showed that both URF and FRF had lower weight gain and SGR and worse feed efficiency than COF. On the other hand, the proximate composition of tilapia fed fermented rice bran was similar to that of commercial compound feed, suggesting that fermented rice bran is a more suitable feed for tilapia than unfermented rice bran. These results suggest that fermented rice bran is a promising feed for tilapia. Future research should investigate the growth-promoting effects of optimising the fermentation conditions and combining it with other feed ingredients. Keywords Fermented rice bran; Nile tilapia; Sustainable aquaculture; Feed formulation; Growth response
Thromboelastography (TEG) is a technique for evaluating the effectiveness of whole blood coagulation. It gives a better picture in line with the cell-based model of hemostasis. Although it is increasingly used in emergency rooms, critical care units, perioperative wards and labour room, the effectiveness of this POCT is not appreciated by the medical community. This retrospective case series analyzed the clinical characteristics of 61 patients who underwent Thromboelastography (TEG) between June 2022 and July 2023 at a tertiary care institution. The most common indication was perioperative assessment during liver transplantation, followed by cytoreductive surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC). TEG offered real-time evaluation of coagulation dynamics, supporting transfusion strategies and aiding in the management of complex bleeding disorders across varied clinical contexts. Distinct and recurring graphical patterns—including the “shallot sign,” “beetroot shoot,” “trophy sign,” and “pebbles on the street”—were observed. Overall, the study underscores TEG’s utility as a point-of-care diagnostic tool in addressing diverse hemostatic challenges. Keywords: Thromboelastography (TEG); Hemostasis; Point of care diagnostics; Coagulation profile; Clinical effectiveness Abbreviations: aPTT: activated Partial Thromboplastin Time; CKH: Citrated Kaolin with Heparinase; CK: Citrated Kaolin; FFP: Fresh Frozen Plasma; INR: International Normalized Ratio; JAK2: Janus Kinase 2; MA: Maximum Amplitude; POCT: Point of Care Testing; PT: Prothrombin Time; R time: Reaction time; ROTEM: Rotational Thromboelastometry; TEG: Thromboelastography; HIPEC: Hyperthermic Intraperitoneal Chemotherapy
Background: The reversal of warfarin in emergency haemorrhage situations is critical for maintaining patient survival. This review evaluates whether four-factor PCC is superior in INR correction and safety when compared with three-factor PCC. Given inconsistent evidence and limited direct comparisons, a meta-analysis was conducted to assess INR reversal, thromboembolic outcomes, and mortality. Study design and method: This systematic review follows PRISMA guidelines to compare three-factor and fourfactor PCC for warfarin reversal in emergency haemorrhagic situations. Literature was gathered from PubMed, Scopus, Google Scholar and Embase, then screened using pre-defined eligibility criteria. Analyses were conducted in Review Manager using mean INR change and risk ratios for thromboembolic and mortality outcomes. Results: From 3,536 literature articles identified from the aforementioned databases, seven retrospective US-based studies met eligibility criteria. The study periods ranged from 2007 to 2015 and primarily assessed INR reversal and thromboembolic outcomes. Study quality was evaluated using the STROBE checklist. The data was analysed and forest plots for mean INR change, thromboembolic outcomes and mortality were generated. Conclusion: The use of four-factor PCC was statistically significant in reducing the INR in warfarin-treated patients experiencing haemorrhage when compared to the use of three-factor PCC. Four-factor PCC showed a greater INR reduction. There was no significant difference observed in both thromboembolic or mortality outcomes between the two groups. However, given the smaller patient populations in the included studies, further research with larger cohorts is warranted to confirm these findings. Keywords: Blood; Haemorrhage; Deep vein thrombosis; Direct oral anticoagulants
The recent European Society for Blood and Marrow Transplantation (EBMT) criteria for diagnosis of Sinusoidal Obstruction Syndrome/Veno-Occlusive disease (SOS/VOD) provided a new classification of “probable” SOS/VOD to improve early diagnosis and ensure prompt therapy with defibrotide. Transient Elastography (TE) and Shear Wave Elastography (SWE) have emerged for early and accurate diagnosis of SOS/VOD after Hematopoietic Stem Cell Transplantation (HSCT). In this review, the author outlined the current knowledge and trends of SOS/VOD in adult patients after HSCT for diagnostic accuracy of Liver Stiffness Measurement (LSM) by elastography. The MEDLINE, PubMed and EMBASE data-bases were systematically accessed for studies using elastography in adult patients after HSCT. In addition, the new biomarker studies for endothelial damage such as VOD check and Circulating Endothelial Cell (CEC) have been also described. Based on the evidence, the increased LSM in the acute phase of SOS/VOD probably may be attributable to the changes caused by inflammation rather than fibrosis. SWE and TE may be potential tools for early accurate diagnosis, disease severity, and follow-up for SOS/VOD. The estimation of endothelial damage using biomarker examination might be a potential procedure for early detection and treatment of SOS/VOD after HSCT.
Pancreatic islet transplantation is a therapeutic option that has great potential for treating Type 1 Diabetes (T1D). However, the number of people with T1D who can benefit from it is limited by the need for 2 or 3 pancreas to treat a patient. In a recent publication, we reviewed the limitations and challenges of successful islet transplantation [1]. Although this information was insightful, it would have been interesting to discuss senescence, a process that can affect the physiology and function of pancreatic islets [2].
Background: Red Blood Cell (RBC) alloimmunisation represents a major complication in transfused Myelodysplastic Syndrome (MDS) patients. Frequent transfusion dependency increases the risk of alloantibody formation, while Hypomethylating Agent (HMA) therapy may have immunomodulatory effects that influence this outcome. This meta-analysis aimed to evaluate the incidence of RBC alloimmunisation in transfused MDS patients and assess the impact of HMA therapy. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Relevant studies were identified through PubMed, Scopus, Embase, and Google Scholar databases. Study quality was assessed using the STROBE checklist. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated for alloimmunisation outcomes using a random-effects model in RevMan 5.4.1. Results: Seven studies published between 2001 and 2024 met the inclusion criteria. The pooled analysis demonstrated a significantly higher risk of RBC alloimmunisation in transfused MDS patients compared with non-MDS controls (OR=1.68; 95% CI 1.13-2.51; P=0.01). A higher transfusion burden was associated with an even greater risk (OR=3.43; 95% CI 1.83-6.43; P=0.0001). HMA-treated MDS patients showed a lower risk compared with untreated controls, though this trend did not reach statistical significance (OR=0.42; 95% CI 0.17-1.03; P=0.06). Conclusion: Transfused MDS patients are at increased risk of RBC alloimmunisation, particularly with higher transfusion exposure. Although not statistically significant, HMA therapy showed a trend toward reducing alloimmunisation, suggesting a potential immunomodulatory effect that requires further investigation. These findings may inform transfusion strategies and guide future research. Keywords Myelodysplastic syndrome; RBC alloimmunisation; Hypomethylating agents; Transfusion; Meta-analysis.
Background: Brincidofovir (BCV) is approved in the US and Canada for the treatment of human smallpox disease in adults and children, including neonates. In long-term storage, the commercially available BCV morphic Form II is slowly converted to a hydrated morphic Form H, which is more stable under ambient conditions. The purpose of this study (NCT05935917) was to compare the Bioequivalence (BE) of the morphic Forms II and H. Methods: This was a Phase 1, open-label, randomized, two-period crossover study completed in healthy adults randomized to receive either a single 100 mg BCV Form II or Form H tablet and followed for 14 days after each dose to assess Pharmacokinetics (PK) and safety. The primary PK endpoints for demonstration of BE were Cmax , AUClast , and AUCinf of BCV in plasma. BE was declared if the 90% Confidence Interval (CI) for the true ratio of test to reference geometric means fell entirely within the range of 0.80 to 1.25 for these endpoints. Results: Forty-four (44) healthy subjects were enrolled, received Form II and Form H treatments, and completed all study visits and safety assessments. For the primary endpoints AUCinf, AUClast , and Cmax, the 90% CIs of the geometric mean ratios for Cmax, AUCinf and AUClast for Form H and Form II fell within the predefined range, thereby demonstrating BE. No new safety signals were identified. Conclusion: Natural conversion of BCV from Form II to Form H over the shelf life does not change the safety or PK profile of BCV in healthy participants. Keywords Brincidofovir; BCV; Bioequivalence; Smallpox; Variola virus
This study investigates environmentally friendly components in Molecularly Imprinted Polymers (MIPs) and their integration into nanocapsules for drug delivery. We developed a novel carrier for MIP-based drugs, enhancing the efficacy of biotherapeutic proteins. Optimizing peptide-based nanospheres with recombinant Fc proteins aims to improve drug delivery efficiency while preserving critical recognition sites. Using X-ray fluorescence microscopy, we analyzed the impact of molecular size and fluctuation movement affect the binding of MIP-based drugs, suggesting that polar additives influence the protein concentrate’s excipient-rich phase. Our drug analysis indicated that the solubility of Cannabidiol (CBD) and monoclonal antibody/insulin combinations increased at 40 °C, which aligns with findings from SEM and thermogravimetric analysis. HPLC-UV and LCMS/MS studies showed effective binding and release of antibody Complementarity Determining Region (CDR) peptides in our delivery system, with a correlation between rapid-release phases and elevated CBD concentrations facilitating protein reabsorption through HSA-imprinted receptors. Higher CBD concentration with anti-IgE antibodies and insulin minimizes target depletion, enhancing CDR persistence and efficacy. The improved drug delivery via nanocapsules enhances FcRn functionality while preserving protein integrity, highlighting its potential for treating chronic diseases and improving patient convenience.
The use of Recirculating Aquaculture Systems (RAS) by governmental agencies to meet stocking needs is becoming commonplace. In South Dakota, the increasing need to grow cool and warm water species such as largemouth bass, bluegill, and channel catfish has necessitated the building of RAS. This paper describes the design, construction, and operation of a RAS built in a storage building at a cold water hatchery without a consistent water source. Each component of the RAS is described in detail and was designed to be cost effective while providing multiple years of service. During operation, the system successfully reared catfish, bluegill, and largemouth bass while maintaining acceptable water quality at 3-5% daily water exchange and minimal oxygen supply (during highest densities) at 2 L/ min of oxygen supply. The operational success of the system may encourage further development of RAS at state hatcheries. Keywords Recirculating Aquaculture System; RAS; Aquaculture
The scale-up of Antiretroviral Therapy (ART) has transformed pediatric and adolescent Human Immunodeficiency Virus (HIV) infection into a manageable chronic disease. Children living with HIV now initiate therapy in infancy and remain on lifelong treatment, resulting in cumulative exposure to antiretrovirals and their toxicities. Hepatotoxicity, ranging from asymptomatic transaminase elevations to severe Drug-Induced Liver Injury (DILI), represents one of the most clinically significant adverse effects of ART. Although hepatotoxicity has been extensively described in adults, pediatric populations face unique vulnerabilities due to developmental pharmacokinetics, nutritional deficiencies, coinfections, and evolving metabolic risk factors during adolescence. This review synthesizes current evidence on mechanisms of ART-related hepatotoxicity, age-specific susceptibilities, and drug class–associated risks in children and adolescents. It further explores the influence of coinfections such as hepatitis B and tuberculosis, emerging challenges including Non-Alcoholic Fatty Liver Disease (NAFLD), and the role of genetic polymorphisms in shaping hepatotoxicity risk. Current recommendations for screening, monitoring, and management are summarized, with a focus on adapting adult-derived protocols to pediatric practice. Gaps in evidence, especially in low and middle-income countries, and priorities for future research including pharmacogenomics, longitudinal studies, and non-invasive biomarkers are highlighted. Pediatric and adolescent patients with HIV represent a vulnerable population in whom hepatotoxicity is both preventable and manageable if recognized early. Optimizing monitoring strategies and developing safer regimens are essential to safeguard long-term liver health in the next generation of people living with HIV.
Hybrid Liposomes (HL), composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (25) dodecyl ether (C12(EO)25), demonstrated significant therapeutic potential against breast cancer cells. HL formed a clear and stable solution with a hydrodynamic diameter of approximately 100nm, which remained unchanged for at least four weeks, suggesting high physicochemical stability suitable for clinical application. In vitro, HL exhibited a marked antiproliferative effect on 4T1-Luc murine breast cancer cells. Furthermore, flow cytometric analysis revealed a significant increase in apoptotic cell populations following HL treatment, indicating that HL effectively induces apoptosis in breast cancer cells. In vivo, administration of HL to 4T1-Luc tumor-bearing mice resulted in a significant reduction in tumor volume and tumor weight, without any observable adverse effects or changes in body weight throughout the treatment period. These findings collectively suggest that HL exert potent growth-inhibitory effects on breast cancer both in vitro and in vivo, and may serve as a promising drug delivery system with minimal toxicity for the treatment of breast cancer.
Schistosomiasis is a neglected tropical disease caused by a parasitic flatworm that is especially prevalent in sub- Saharan Africa. Schistosomiasis has debilitating symptoms that ultimately have negative implications for socioeconomic activities in endemic areas, making access to treatments critically important for long-term health. This thesis focuses on the importance of three rural plants and their medicinal uses for schistosomiasis in a rural Ugandan village. The plants known as Kisanasana, Lubilzi, and Niimu are locally used to treat intestinal symptoms of schistosomiasis and have been reported to have positive results. A study was conducted in the village of Mpunde and surrounding areas to document the knowledge, attitudes, and practices of local villagers surrounding local soiltransmitted helminthic infections. However, the use of non-biomedical treatments to control parasitic infections remains critically understudied. This thesis therefore makes an important contribution to understanding traditional healing practices with plants that are less well known and poorly studied in Western ethnobotany. Keywords Schistosomiasis; Ethnobotany; Medicinal plants; Bitter leaf; Neem; Uganda
Background: Nemolizumab is a monoclonal antibody that targets the receptor alpha of the neuro-immune cytokine IL-31. This clinical PK bridging study was conducted to support the marketing application of the prefilled dual chamber pen. Methods: This was a phase 1, randomized, multicenter, open-label, single-dose, parallel-group study in healthy adult subjects. Participants (N=192) were randomized by device (pen or syringe) and by injection site (abdomen, thigh, arm) and received one subcutaneous 60 mg nemolizumab dose. The primary endpoint pharmacokinetic parameters were analyzed using a linear mixed-effect model. Safety data were summarized descriptively. Results: Mean age was 41.5 years (19 to 65 years), mean body weight was 72.76 kg (45.4 to 107.4 kg) and 61% of participants were female. The geometric least-square mean ratio comparing pen versus syringe was 105.90% for Cmax and 97.69% for AUC0-∞. The associated 90% confidence intervals fall within the 80.00%-125.00% bioequivalence range. No treatment-emergent anti-drug antibodies were detected with the pen. Treatment emergent adverse events were experienced by 56% and 43% of subjects in the syringe and the pen groups, respectively and were primarily mild or moderate in severity. Conclusions: Single dose of nemolizumab administered as new formulation presentation (pen) was bioequivalent to the prefilled dual chamber syringe used in Phase 3 clinical studies. Nemolizumab delivered subcutaneously by pen or syringe was well tolerated, and no new safety risks were identified with the pen. Hence, results from this PK bridging study support the pen presentation as the commercial drug product. Nemolizumab; Pharmacokinetics; Healthy subjects; Prefilled pen; Dual chamber syringe
Metabolic Syndrome (MetS) has evolved from a purely metabolic entity to a complex immunometabolic disorder in which chronic low grade inflammation, adipokine imbalance and oxidative stress play major roles. Recent evidence, including our cross-sectional study of 504 Turkish adults, showed that 32.7% met MetS criteria and 15.5% exhibited positive autoimmune markers (ENA/FANA) without overt autoimmune disease. This review highlights the pancreas as a central organ influenced by both metabolic overload and immune activation, emphasizing early detection opportunities to prevent β-cell dysfunction and autoimmune pancreatitis.
