Therapeutic Advantage Research Articles

Postprandial changes to systemic metabolism imprint durable changes on T cell immune responses

Abstract Here we show short periods of fasting and refeeding can have long-lasting effects on T cell immunity. Mouse or human T cells from fed hosts have higher mitochondrial quality and respiratory capacity than those from fasted hosts ex vivo. These metabolic phenotypes persist after activation and expansion, both in vitro culture and in vivo in response to vaccination. Fed T cells outcompete fasted T cells in a co-transfer model, such that T cells from fasted hosts form far fewer memory T cells. Serum profiling revealed triglycerides as a driver of postprandial metabolic reprogramming: chylomicrons enriched from the lymphatics of fed mice were sufficient to enhance mitochondria of fasted T cells. LDLR-deficient T cells had the metabolic phenotype of fasted T cells and were insensitive to fed serum, confirming the role of triglyceride uptake in postprandial T cell metabolic programming. Transcriptomic analysis revealed higher expression of LDLR, OXPHOS proteins, and fatty acid metabolism enzymes in fed T cells over fasted T cells. Finally, human CAR T cells manufactured from the same donor after a meal show a therapeutic advantage over T cells collected in the fasted state. In summary, postprandial metabolism imparts durable metabolic and functional advantage on T cells. Our study highlights the need to consider diet content and timing as key factors in immune cell analysis, vaccination strategies, and the generation of cellular therapies for cancer.

Control of seizure-like dynamics in neuronal populations with excitability adaptation related to ketogenic diet.

We consider a heterogeneous, globally coupled population of excitatory quadratic integrate-and-fire neurons with excitability adaptation due to a metabolic feedback associated with ketogenic diet, a form of therapy for epilepsy. Bifurcation analysis of a three-dimensional mean-field system derived in the framework of next-generation neural mass models allows us to explain the scenarios and suggest control strategies for the transitions between the neurophysiologically desired asynchronous states and the synchronous, seizure-like states featuring collective oscillations. We reveal two qualitatively different scenarios for the onset of synchrony. For weaker couplings, a bistability region between the lower- and the higher-activity asynchronous states unfolds from the cusp point, and the collective oscillations emerge via a supercritical Hopf bifurcation. For stronger couplings, one finds seven co-dimension two bifurcation points, including pairs of Bogdanov-Takens and generalized Hopf points, such that both lower- and higher-activity asynchronous states undergo transitions to collective oscillations, with hysteresis and jump-like behavior observed in vicinity of subcritical Hopf bifurcations. We demonstrate three control mechanisms for switching between asynchronous and synchronous states, involving parametric perturbation of the adenosine triphosphate (ATP) production rate, external stimulation currents, or pulse-like ATP shocks, and indicate a potential therapeutic advantage of hysteretic scenarios.

Guideline for diagnosis and treatment of recurrent spontaneous abortion with integrated traditional Chinese and western medicine

Recurrent spontaneous abortion is one of the most common pregnancy complications in obstetrics and gynecology. The normative diagnosis and treatment of recurrent spontaneous abortion has become an important problem to be solved urgently in the field of reproductive health. The integrated traditional Chinese and western medicine provides a safe and effective treatment method for recurrent spontaneous abortion, but there is no guideline for diagnosis and treatment of recurrent spontaneous abortion with integrated traditional Chinese and western medicine. The guideline is based on the requirements of World Health Organization(WHO) handbook for guideline development and follows the principles of evidence-based medicine. Through literature pre-search, expert interviews, clinical research, and conference consensus, 16 clinical problems are identified in this guideline. PICO principles are used for evidence retrieval, screening, and synthesis. The evidence quality is evaluated for the included evidence bodies. Recommendation opinions and consensus suggestions are formed through three rounds of the Delphi expert questionnaire survey. An expert meeting is held to finalize the draft. The opinions of experts in traditional Chinese medicine, western medicine, integrated traditional Chinese and western medicine, methodology and pharmacy are widely solicited. The guideline contains five parts: scope, term and definition, diagnosis, treatment, and diagnosis and treatment flow chart of integrated traditional Chinese and western medicine. There are corresponding recommendations and summaries of evidence for clinical problems related to the diagnosis and treatment of integrated traditional Chinese and western medicine. This guideline is guided by clinical problems, combining disease differentiation and syndrome differentiation and integrating pre-pregnancy regulation and treatment and post-pregnancy preservation, highlighting the therapeutic advantages of integrated traditional Chinese and western medicine, so as to further standardize the clinical diagnosis and treatment of recurrent spontaneous abortion and promote the diagnosis and treatment level of integrated traditional Chinese and western medicine for recurrent spontaneous abortion.

Changing Concepts About Optimal Target Blood Pressure and the Therapeutic Advantages of Azilsartan for Achieving it

The article discusses current issues of the treatment of arterial hypertension. According to presented data, so-called therapeutic nihilism is becoming one of the main barriers to achieving target blood pressure (BP). This nihilism is that despite evidence of the effectiveness of achieving lower BP values, practitioners do not intensify antihypertensive therapy sufficiently to achieve such values. The article specially addresses new criteria for the effectiveness of antihypertensive therapy, which reflect the therapy sustainability. The most commonly used indicator is the duration of the period, during which systolic BP remains in the therapeutic range. The prognostic significance of such indicators is discussed. In these conditions, it is very important to use the most effective antihypertensive drugs for initial antihypertensive therapy, including as a part of combination therapy. This tactic provides more frequent achievement of BP goals without the need for dose adjustment. In this regard, a systematic review was performed, which included sufficiently large randomized studies of the antihypertensive effectiveness of azilsartan medoxomil. This systematic review will provide comprehensive information on a possible role of using the angiotensin II receptor blocker azilsartan as a basic drug for the treatment of a wide range of patients with high BP. Most of the studies included in the systematic review assessed the effectiveness of combination therapy including azilsartan.

Small extracellular vesicles derived from human mesenchymal stem cells prevent Th17-dominant neutrophilic airway inflammation via immunoregulation on Th17 cells

Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.

Synthetic cationic helical polypeptides for the stimulation of antitumour innate immune pathways in antigen-presenting cells.

Intracellular DNA sensors regulate innate immunity and can provide a bridge to adaptive immunogenicity. However, the activation of the sensors in antigen-presenting cells (APCs) by natural agonists such as double-stranded DNAs or cyclic nucleotides is impeded by poor intracellular delivery, serum stability, enzymatic degradation and rapid systemic clearance. Here we show that the hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate innate immune pathways via endoplasmic reticulum stress in APCs. One of the three polypeptides that we engineered activated two major intracellular DNA-sensing pathways (cGAS-STING (for cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes) and Toll-like receptor 9) preferentially in APCs by promoting the release of mitochondrial DNA, which led to the efficient priming of effector T cells. In syngeneic mouse models of locally advanced and metastatic breast cancers, the polypeptides led to potent DNA-sensor-mediated antitumour responses when intravenously given as monotherapy or with immune checkpoint inhibitors. The activation of multiple innate immune pathways via engineered cationic polypeptides may offer therapeutic advantages in the generation of antitumour immune responses.

Two-dimensional MXene-based nano-prodrug for synergistic chemo-photothermal therapy on cancer treatment

In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti3C2Tx MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti3C2Tx-DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti3C2Tx was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti3C2Tx. The high surface area of Ti3C2Tx could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body's bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti3C2Tx MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.

Therapeutic advantage of teriparatide in very elderly patients with proximal femoral fractures: a functional and BMD analysis

BackgroundTeriparatide, a recombinant parathyroid hormone, is pivotal in osteoporosis treatment, particularly in post-surgical recovery for hip fractures. This study investigates its efficacy in functional recovery post-hip fracture surgery in elderly patients, a demographic particularly susceptible to osteoporotic fractures.MethodsIn this retrospective cohort study, 150 elderly patients with proximal femoral fractures undergoing open reduction and internal fixation were enrolled. They were categorized into two groups: receiving 20 µg of daily teriparatide injections for 18 months and receiving standard antiresorptive medications during a 24-month follow-up. Detailed records of patient demographics, Fracture Risk Assessment Tool scores, and comorbidities were kept. Key outcomes, including bone mineral density (BMD) and functional scores (Barthel Index and Visual Analog Scale for hip pain), were evaluated at 3 and 24 months post-surgery.ResultsOut of the original cohort, 126 patients (20 men and 106 women with an average age of 85.5 ± 9.3 years) completed the study. The teriparatide group exhibited significant enhancements in both functional scores and BMD when compared to the control group. Notably, functional improvements were less pronounced in male patients compared to female patients. Additionally, the incidence of new fractures was markedly lower in the teriparatide group.ConclusionAdministering teriparatide daily for 18 months post-surgery for proximal femoral fractures significantly benefits very elderly patients by improving functionality and bone density, with observed differences in recovery between genders. These results reinforce the efficacy of teriparatide as a potent option for treating osteoporosis-related fractures in the elderly and highlight the importance of considering gender-specific treatment and rehabilitation strategies.

Conservative management of proximal hamstring avulsion: A clinical study

IntroductionThe management of proximal hamstring tear (PHT) is debated and consensus regarding recommended measures and individual treatment regimens is lacking. The present investigation evaluated the efficacy of a conservative management of partial and complete PHT. MethodsThe present observational study was conducted following the STROBE statement. In June 2018 the medical databases of the BG Klinikum Bergmannstrost Halle, Germany were accessed. All the patients with PHT were retrieved. The outcomes of interest were to evaluate the clinical examination, PROMs, imaging, and isokinetic muscle strength at the baseline and last follow-up. Results31 patients were enrolled in the present study. Nine patients (29 % (9 of 31) described local pain at the ischial tuberosity in sitting situations and also in manual palpation. A persistent gap in the tendon string beneath the tuberosity in manual palpation was reported in 25.8 % (8 of 31). The mean VAS at the last follow-up was 2.3 ± 2.3. The mean LEFS score was 50.9 ± 18.8.Control MRI at follow-up showed scarring restitution in the proximal tendon in all patients in the partial tear group. In the complete tear group, a persisting defect state of the proximal tendon course was found in 45 % (9 of 20). The injured side achieved 81.5 ± 22.2 % of the force of the uninjured side, measured in the flexion movement at 60°/s. At an angular velocity of 240°/s, 83.2 ± 26.3 % of the force of the uninjured side was achieved. ConclusionAccording to the main findings of the present study, conservative therapy of PTH tears is associated with good clinical outcomes. High-quality investigations are required to establish the proper therapeutic algorithm and advantages of conservative management compared to a surgical approach. Level of evidenceLevel III.

The Role of Lactobacillus Reuteri Probiotic for Preventing Functional Gastrointestinal Disorders in Toddlerhood

Probiotic<i> Lactobacillus </i>reuteri has been shown to be useful for a number of gastrointestinal disorders. Its ability to secrete antimicrobial compounds, prevent pathogenic microorganisms from colonizing the host, and alter the composition of the commensal microbiota in the host are all major contributors to its therapeutic advantages. Not only that, but L. reuteri treatment strengthens the host's defenses against infection and pro-inflammatory cytokine production while enhancing the growth and functionality of regulatory T cells. Numerous pediatric illnesses, particularly those pertaining to the intestinal health of infants, have been found to be well managed by L. reuteri, according to systematic reviews and meta-analyses. According to current research on L. reuteri, it may be useful in the management and avoidance of a number of common clinical disorders, including functional constipation, infantile colic, regurgitation, and diarrhea. Probiotic treatment for pediatric illnesses has had favorable benefits on bowel regularity in individuals with chronic constipation and has been found to successfully reduce screaming and/or fussing time in newborns with colic. Additionally, it quickens the emptying of the stomach and lessens distension. Several research have even come to the conclusion that this probiotic strain reduces the frequency of regurgitation. The potential of this probiotic strain for application in the treatment of several gastrointestinal disorders is evident from all of these findings. Therefore, this study aims to encapsulate and condense the advantages of this probiotic strain in clinical settings, with a particular emphasis on how it supports babies' and toddlers' immune systems and gut health.

Synthesis, structural, multitargeted molecular docking analysis of anti-cancer, anti-tubercular, DNA interactions of benzotriazole based macrocyclic ligand

Biologically important macromolecule 1, 1′, 3, 3′ Bis − [2,3,5,6-Tetramethyl-p-phenylenebis(methylene)] dibenzotriazlinium dibromide hydrate (BTD) was synthesized and characterized using FT-IR, NMR and single-crystal XRD (SCXRD). SCXRD revealed that the compound was crystallized as a monoclinic system and associated through weak intermolecular interactions like H-bonding and π- π stacking interactions. These weak intermolecular interactions in BTD were studied using Crystal Explorer and Gaussian. The calculated energies for the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) showed the stability and reactivity of the title compound. Molecular electrostatic potential (MEP) surface analysis was used to investigate the crystal’s nucleophilic and electrophilic reactive sites. The molecular shape and intermolecular interactions in the crystal structure were determined using Hirshfeld surface analysis and fingerprint plots. Anticancer, anti-bacterial and DNA binding ability of BTD were investigated by experimental and theoretical techniques. The obtained results suggest that BTD possesses better anti-cancer, anti-bacterial and DNA binding abilities. The mode of action of antibiotic and anticancer approach was discussed. This provides promising therapeutic advantages for further development.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

The contemplation of amylosefor the delivery of ulcerogenic nonsteroidal anti-inflammatory drugs.

This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked withnonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility andbiodegradability, as well asits capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.

Alzheimer's Disease Immunotherapy: Current Strategies and Future Prospects.

Alzheimer's disease (AD) is an extremely complex and heterogeneous pathology influenced by many factors contributing to its onset and progression, including aging, amyloid-beta (Aβ) plaques, tau fibril accumulation, inflammation, etc. Despite promising advances in drug development, there is no cure for AD. Although there have been substantial advancements in understanding the pathogenesis of AD, there have been over 200 unsuccessful clinical trials in the past decade. In recent years, immunotherapies have been at the forefront of these efforts. Immunotherapy alludes to the immunological field that strives to identify disease treatments via the enhancement, suppression, or induction of immune responses. Interestingly, immunotherapy in AD is a relatively new approach for non-infectious disease. At present, antibody therapy (passive immunotherapy) that targets anti-Aβ aimed to prevent the fibrillization of Aβ peptides and disrupt pre-existing fibrils is a predominant AD immunotherapy due to the continuous failure of active immunotherapy for AD. The most rational and safe strategies will be those targeting the toxic molecule without triggering an abnormal immune response, offering therapeutic advantages, thus making clinical trial design more efficient. This review offers a concise overview of immunotherapeutic strategies, including active and passive immunotherapy for AD. Our review encompasses approved methods and those presently under investigation in clinical trials, while elucidating the recent challenges, complications, successes, and potential treatments. Thus, immunotherapies targeting Aβ throughout the disease progression using a mutant oligomer-Aβ stimulated dendritic cell vaccine may offer a promising therapy in AD.

Enhanced Biocompatibility by Evaluating the Cytotoxic and Genotoxic Effects of Magnetic Iron Oxide Nanoparticles and Chitosan on Hepatocellular Carcinoma Cells (HCC)

Hepatocellular carcinoma (HCC), the fifth most prevalent cancer worldwide, is influenced by a myriad of clinic-pathological factors, including viral infections and genetic abnormalities. This study delineates the synthesis, characterization, and the biological efficacy of iron oxide nanoparticles (Fe3O4) and chitosan-coated iron oxide nanoparticles (Fe3O4-CS) against HCC. Analytical methods confirmed the successful synthesis of both nanoparticles, with Fe3O4-CS demonstrating a smaller, uniform spherical morphology and distinct surface and magnetic properties attributable to its chitosan coating. The prepared materials were analyzed using various techniques, and their potential cytotoxic effects on HepG2 cancer cells line for HCC were investigated. In biological evaluations against HepG2 cells, a notable distinction in cytotoxicity was observed. Fe3O4 showed modest anticancer activity with an IC50 of 383.71 ± 23.9 µg/mL, whereas Fe3O4 exhibited a significantly enhanced cytotoxic effect, with a much lower IC50 of 39.15 ± 39.2 µg/mL. The Comet assay further evidenced Fe3O4-CS potent DNA damaging effect, showcasing its superior ability to induce apoptosis through extensive DNA fragmentation. Biochemical analyses integrated into our results reveal that Fe3O4-CS not only induces significant DNA damage but also markedly alters oxidative stress markers. Compared to control and Fe3O4-treated cells, Fe3O4-CS exposure significantly elevated levels of oxidative stress markers: superoxide dismutase (SOD) increased to 192.07 U/ml, catalase (CAT) decreased to 0.03 U/L, glutathione peroxidase (GPx) rose dramatically to 18.76 U/gT, and malondialdehyde (MDA) levels heightened to 30.33 nmol/gT. These results underscore the potential of Fe3O4-CS nanoparticles not only in inducing significant DNA damage conducive to cancer cell apoptosis but also in altering enzymatic activities and oxidative stress markers, suggesting a dual mechanism of action that may underpin their therapeutic advantage in cancer treatment. Our findings advocate for the further exploration of Fe3O4-CS nanoparticles in the development of anticancer drugs, emphasizing their capability to trigger oxidative stress and enhance antioxidant defense mechanisms.

Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation, posing challenges in the development of effective treatments. Nuciferine, an alkaloid found in lotus leaf, has shown promising anti-inflammatory and anti-tumor effects, yet its efficacy in RA treatment remains unexplored. This study investigated the antiproliferative effects of nuciferine on the MH7A cell line, a human RA-derived fibroblast-like synoviocyte, revealing its ability to inhibit cell proliferation, promote apoptosis, induce apoptosis, and cause G1/S phase arrest. Additionally, nuciferine significantly reduced the migration and invasion capabilities of MH7A cells. The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis (CIA) rat model, where it markedly alleviated joint swelling, synovial hyperplasia, cartilage injury, and inflammatory infiltration. Nuciferine also improved collagen-induced bone erosion, decreased pro-inflammatory cytokines and serum immunoglobulins (IgG, IgG1, IgG2a), and restored the balance between T helper (Th) 17 and regulatory T cells in the spleen of CIA rats. These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

The Trajectory of Haptoglobin in Haemolysis, Inflammation and Transfusion Reaction

Introduction: Haptoglobin is an acute-phase α2-glycoprotein produced in the liver with the major biological function of binding free haemoglobin with very high affinity to prevent the loss of iron following hemolysis. Haptoglobin has an anti-inflammatory property and is raised during inflammation whereas, low level is associated with haemolysis. Transfusion is linked with haemolysis thereby increasing the level of free haemoglobin due to anti-haptoglobin and storage effect. Studies have revealed interplay of haptoglobin in haemolysis, inflammation and transfusion reaction although, the underlying mechanism is not well understood. Besides, its utilization as a diagnostic biomarker and therapeutic advantage have not been well explored hence, this study. Method: In this review 20 primary studies from various electronic databases such as Google scholar, Semantic scholar and PubMed were obtained on the basis that they were focused on haptoglobin, haptoglobin in haemolysis, inflammation and transfusion. This was made possible by the use of Boolean function. Results: Haptoglobin, is measured in blood due to its complex formation with hemoglobin, forming a protective non-covalent complex with CD63 as receptor. The finding from this review shows that, haptoglobin plays a crucial role in scavenging surplus hemoglobin, iron and heme in haemolysis with antioxidant function and immunomodulatory effect in transfusion reactions. The concept of the trajectory of haptoglobin explored the multi-dimensional course of this acute phase scavenger protein in the course of clinical conditions of haemolysis, inflammation and transfusion reaction. The review confirmed specific roles of haptoglobin such as physiologic-antioxidant, prognostic, diagnostic biomarker, immunologic and therapeutic. Additionally, an inverse relationship exists between haptoglobin and haemolysis as well as transfusion reaction consequent to hypohaptogloinaemia whereas, direct relationship exists with inflammation resulting to hyperhaptoglobinaemia observed in those clinical conditions respectively. Haptoglobin synthesis is elevated by the liver in response to inflammation, countering oxidative damage and inflammation by neutralizing free hemoglobin. When there is an immunological mismatch, haemolytic transfusion reactions can occur and transfusion of prolonged stored blood potentiate same effect. Conclusion: The role of haptoglobin cannot be overemphasized. Based on the widespread roles and clinical relevance of haptoglobin, it is vital that haptoglobin be utilized

Role of Cinnamomum verum leaves in the management of Vascular dementia: A comprehensive overview

Spices are utilized for both culinary and medicinal purposes and have been for a very long time originating from Sri Lanka and southern India, Cinnamomum verum may also be found in other Asian, Caribbean, Australian, and African countries. The principal compounds contained are Cinnamaldehyde and Eugenol, both of which have unique medicinal qualities in the leaves of Cinnamomum verum. Cinnamonaldehyde (CA), a bioactive phytochemical offer therapeutic advantages against the beginning of cardiovascular illnesses. Eugenol is an organic compound found in the leaves of Cinnamomum verum. Eugenol has antihypercholesterolemic and antiatherogenic effects. Eugenol's smooth muscle relaxant effect is due to its inhibition of receptor-operated and voltage-sensitive channels. Endothelial cells create nitric oxide (NO), which relaxes blood vessels. Eugenol has substantial anti-inflammatory properties. The antipyretic activity of eugenol is well recognized, since it reduces fever by reducing prostaglandin and sodium archidonate synthesis. Eugenol's hydrophobic nature allows it to pass the blood-brain barrier and enter the brain. Eugenol protects neuronal cells against the oxidative and excitotoxic effects of N-methyl-D-aspartate (NDMA). Eugenol has neuroprotective properties in hippocampal tissues due to its capacity to reduce brain-derived neurotrophic factor (BDNF) and postpone amyloid β -peptide (A- β) induced cell death via abnormal Ca2+ blocking. Anti-hypertensive property of Eugenol is known as it has the ability to activate TRPV channels and to relax endothelium-depleted arteries. Eugenol, which is found in Cinnamomum verum leaves, has been shown to be beneficial in the control of hypertension and so may be beneficial in the management of vascular dementia.

Regional Differences in GLP-1 Receptor Agonists Related Biliary Disease: A Pharmacovigilance Study of VigiBase®

Glucagon-like peptide-1 receptor agonists are highly recommended for treatment of type 2 diabetes as one of the second-line therapies with additional benefits of cardiorenal disease. Despite the diverse therapeutic advantages, safety issues remain controversial regarding the pancreatic-related adverse events associated with the use of incretin-based drugs. We aimed to examine regional differences in biliary diseases related safety for GLP-1 RAs compared with all other antidiabetic drugs. In this study, individual case safety reports for GLP-1 RAs and comparison group were retrieved from the World Health Organization’s global database, VigiBase during 2005 to 2023. Disproportionality analysis was performed to examine Reporting odds ratio and 95% confidence interval for each adverse event of interest, adjusted for sex and age group by using logistic regression. Disproportionate reporting was observed in America for biliary track disorders associated with the GLP-1 RAs compared with all other antidiabetic drugs. However, for gallbladder-related disorders, an increased risk was identified in most regions (America: ROR 2.34; 95%CI 2.06-2.66, Europe: ROR 5.71; 4.62-7.05, Asia: ROR 4.12; 2.98-5.69). As this study cannot determine the causality between GLP-1 RAs and the biliary disease, a multinational confirmatory study is inevitable to validate the regional differences in the association between GLP-1 RAs and biliary disease.

Therapeutic advantages of omega-3 fatty acid supplementation in patients with schizophrenia – a systematic review

Introduction and aim. In patients with schizophrenia, omega-3 (n-3) polyunsaturated fatty acids (PUFAs) treatment was found to ameliorate the cardiovascular, metabolic, and inflammatory problems caused by antipsychotic medication and even reduce the need for medication by 20%. In this study, we evaluated the potential therapeutic effects of n-3 PUFA supplementation in patients with schizophrenia. Material and methods. The PRISMA guidelines were followed in conducting this systematic review. The Embase, MEDLINE, Web of Science, and Google Scholar databases were searched electronically. The first search yielded 50 papers in total. Subse quently, 43 publications that did not meet our eligibility requirements were removed, and seven articles were selected. Analysis of the literature. The analysis showed that n-3 PUFA supplementation and the placebo group both decreased their psychotic (PANSS and GAF scales) and Calgary Depression Scale symptomatology and boosted their functional ability (GAF) when used as an adjuvant to antipsychotic medication. When administered as a monotherapy with a metabolic antioxidant, n-3 PUFA supplementation proved beneficial for treating schizophrenia. In patients with schizophrenia, n-3 PUFAs have thera peutic benefits as adjuvant treatments to medications, although not for different variables or patient groups. Conclusion. In many studies, patients with chronic schizophrenia who received n-3 PUFA supplementation showed no improvement in their clinical condition.