Destruction Of Red Blood Cells Research Articles

Advancements in PNH treatment: Crovalimab’s clinical efficacy

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, life-threatening hematologic disease which is characterized by the destruction of red blood cells, leading to a range of severe symptoms and complications. Recent advancements in drug therapies have significantly improved the prognosis for PNH patients. This editorial comprises the impact of PNH drugs, focusing on eculizumab and ravulizumab and comparing it to the recently approved complement inhibitor, crovalimab which targets the complement system to prevent hemolysis. The discussion includes an analysis of clinical trial data and patient outcomes. The editorial mainly addresses emerging therapies like Crovalimab, that promise to offer more comprehensive, complete blockage of complement system and low-dose solutions reducing the treatment hassle while simultaneously appealing to a wider range of patients.

Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia

Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in two cohorts, one for patients with CAD and the other wAIHA. In each cohort, patients were randomly assigned to receive 270 or 360 mg/day pegcetacoplan for up to 48 weeks. Safety endpoints included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy endpoints included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale. Thirteen (100%) and 10 out of 11 (91%) patients with CAD and wAIHA respectively experienced at least 1 TEAE. Ten patients had at least 1 serious adverse event; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90 to 3.00) and 1.7 g/dL (-1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective in patients with CAD and wAIHA. Registered at www.clinicaltrials.gov (NCT03226678).

An immuno-inflammatory profiling of asymptomatic individuals in a malaria endemic area in Uganda

Malaria caused by Plasmodium falciparum leads to the destruction of red blood cells (RBCs). A better understanding of how naturally immune individuals control infections should be valuable for future vaccine studies. Antibodies against RBCs and RBC surface antigens were measured together with different inflammatory markers in healthy adults living in a malaria endemic area of Uganda and compared to Swedish healthy adults. Antibodies binding to RBCs were clearly elevated in Ugandans compared to Swedish samples, and for RBC surface antigens the Ugandans had higher levels of antibodies against JMH, but not against Cromer or Kell. Twenty-eight percent of the Ugandans were PCR-positive for P. falciparum, and these had higher levels of IgG against parasite extract and more inhibition in functional growth/invasion assays, but levels of antibodies against RBC, RBC surface antigens, results from Direct Antiglobulin Tests (DAT) and indirect antiglobulin tests were similar when compared with PCR-negative individuals. When inflammatory markers (α-1-antitrypsin, haptoglobin, orosomucoid/α-1-acid glycoprotein, CRP, IgG, IgA and IgM) were measured there were in general almost no signs of inflammation except for clearly elevated levels of IgG. Some had low levels of haptoglobin and for orosomucoid more than half of the individuals had clearly reduced levels. There was no correlation between the inflammatory markers and PCR-positivity, antibodies against RBCs or parasites. In conclusion, for healthy adults living in a malaria endemic area, there was a clear presence of antibodies against RBCs in parallel with high levels of IgG and almost no signs of inflammation, even though many individuals were carrying parasites.

Synthesis and antimicrobial activity of yttrium-doped cerium oxide nano-composite against wound pathogen

Abstract Nanocomposite materials have attracted considerable interest in several disciplines owing to their distinctive characteristics and possible uses. The primary objective of this study was to synthesize and characterize a nanocomposite material consisting of cerium that has been doped with yttrium. The shape, structure, and properties of the synthesized nanocomposite was characterized using various characterization techniques including ultraviolet spectrophotometry, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), zeta potential measurements, dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR).The antibacterial activity of the nanocomposite was assessed against a range of pathogenic bacteria including Gram-positive bacteria - Enterococcus faecalis, Staphylococcus aureus, and Gram-negative bacteria- Escherichia coli, Pseudomonas aeruginosa using standard microbiological techniques. The results indicate that the nanocomposite possesses strong antibacterial properties against a wide range of microorganisms, showcasing its potential as a highly effective antimicrobial agent for diverse applications in the biological, environmental, and industrial fields. Hemolysis is the process of red blood cell destruction, resulting in the release of hemoglobin into the surrounding fluid. In this study, 0.7:0.3M nanocomposite had showed effective biocompatibility with less than 5%. Furthermore, this particular composite remained identical in different time intervals, while other composites would normally fluctuate. Research has shown that meticulous material design and surface modification can reduce the harmful effects on red blood cells, hence improving the safety of nanocomposite for therapeutic purposes. In summary, this study offers valuable information on the creation, analysis, and assessment of nanocomposite materials with antimicrobial properties.

Correlation Crossmatching Test with Effectiveness of Transfusion in Hemolytic Anemia Patients

Hemolytic anemia is anemia caused by the premature destruction of red blood cells. Transfusion with hemolytic anemia is a dilemmatic indication and is still based on clinical decisions. Several studies assessed the effectiveness of transfusions in hemolytic anemia patients with incompatible crossmatching showed effectiveness. This study aimed to analyze crossmatching with transfusion effectiveness in hemolytic anemia patients. Retrospective cohort observational study with medical record data from January 2019 to May 2022 of hemolytic anemia patients who got transfusion therapy. The variables included age, gender, hemoglobin levels before and after transfusion, crossmatching test, and transfusion effectiveness based on increased hemoglobin after transfusion 1 g/dL of 1 Pack Red Cell (PRC) unit. One hundred three (103) patients with hemolytic anemia 45 received PRC, 12 males (26.7%) and 33 females (73.3%). Ages 19 - < 45 years subjects had the most transfusions. Hemoglobin levels before and after transfusion showed significant differences (p-value =0.000) in the patients with a diagnosis of hereditary, unspecified, and autoimmune hemolytic anemias. The correlation between the effectiveness of transfusions with gender and age was not found (p=0.521, p=0.240). The correlation between crossmatching with the effectiveness of transfusion was not found (p=0.089). Hemolytic anemia patients with transfusion showed an increase in hemoglobin levels between before and after transfusion even with incompatible crossmatching. The correlation between the results of crossmatching with transfusion effectiveness in patients with hemolytic anemia was not found. Good premedication treatment can provide effective transfusion.

A-153 Study of the evaluation of fragment flag and percentage schistocyte count in MINDRAY® BC-6800 PLUS in a public pediatric hospital in Argentina

Abstract Background Schistocytes are fragmented red blood cells (FRCs) that arise from the mechanical destruction of red blood cells (RBCs). They indicate the possible presence of a thrombotic microangiopathy (TMA). TMA includes hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura(TTP). ICSH defined schistocytes as 4 well stablish shapes always smaller than intact RBCs. The gold standard for the identification of schistocytes is microscopic evaluation. A schistocyte count should be considered clinically meaningful if it represent the main morphological RBCs abnormality in the periferic blood smear (PBS). The results should be expressed as a percentage, after counting at least 1000 RBCs in optimal areas of the PBS. The cut off for TMA was previously stablished in above 1% (adult population) and a higher percentaje in pre term newborns (above 5%). Some blood cell count analyzers have a flag for FRC, and some of them also provide methods for an automated FRC count, through the measurement of forward scatter and the intensity of fluorescence or 2-dimensional optical analysis. The Mindray® BC 6800 PLUS provides a flag for fragments and the research FRC% parameter that quantifies fragmented RBCs. When the flag and the FRC% are combined, can bring value to diagnostic TMA. Objetives Evaluate the sensitivity and specificity of the fragment flag to predict schistocyte on the PBS of pediatric samples. Evaluate the utility of FRC% as TMA diagnostic tool and compare with the gold standard. Methods 725 pediatric samples were analyzed (0-18 years).16 of them was patient samples diagnosed with TMA. All blood cell counts were determined using Mindray®BC-6800 PLUS. Cut off 1% was considered for FRC% in TMA. Inclusion criteria for TMA samples include thrombocytopenia, increased lactate dehydrogenase and decreased hemoglobin concentration. Schistocyte counting was carried out from May-Grunwald-Giemsa-stained PBS according to the recommendations proposed by ICSH. Only ICSH established shapes were kept as valid. Results Regarding the sensitivity of the fragment flag, it was 84.62% with a specificity of 91.13% to detect the presence of schistocytes in PBS samples. In the Bland-Altman analysis, the FRC% shows a difference with a tendency to underestimation with respect to the observation on the PBS, which was less at lower percentages of schistocytes. The sensitivity of the FRC% to TMA was 75% while the specificity was 94.36% and a negative predictive value (NPV) of 99.41%. Conclusions Fragments flag represents a potentially powerful tool for screening of squistocytes in pediatric samples. Although sensibility and NPV for FRC% authomatical counts were acceptable, a few false-negative samples were found. Presence of FRC% below a threshold of 1% could exclude TMA.However PBS microscopic observation is still the gold standard to determine squistocytes presence. For the purpose of complete our study and to get further larger scale prospective data, we started collecting all data for all samples entering the laboratory in order to improve an authomatical method that should have a more rapid turn-around time at lower costs.

How do we manage hyperhemolysis syndrome.

Hyperhemolysis syndrome (HHS) is a catastrophic anemia characterized by destruction of both donor and patient red blood cells (RBC). HHS occurs after transfusion and can cause significant morbidity and mortality. Given the difficulty in diagnosing and managing this process, we provide a detailed overview of our treatment protocol. Members of the Transfusion Medicine and Hematology faculty at our institution collaborated in an iterative process to produce a consensus approach to patients with HHS. We present diagnostic criteria for HHS: recent transfusion within past 7 days (up to 21 days), rapid hemoglobin decline to below the pretransfusion level (usually hemoglobin drop >25% from pretransfusion), a significant decrease in HbA% (in patients with sickle cell disease or beta thalassemia), low or decreasing reticulocyte count in a patient with worsening anemia, and laboratory evidence of hemolysis. We also describe an in-depth approach to management focusing on optimizing hematopoiesis while dampening the immune response. We provide a comprehensive approach to the diagnosis and management of HHS based on contemporary literature and clinical experience designed to optimize outcomes for patients.

Assessment of Reticulocyte Count as a Prognostic Indicator for Canine Ehrlichiosis: Implications for Diagnostic and Therapeutic Strategies

Canine ehrlichiosis is increasingly recognized in India, with significant implications for canine health. It is a tick-borne disease, caused by Ehrlichia canis. It is prevalent in various regions, particularly in areas with high tick populations. Anaemia is one of the most common and important manifestation of this disease. Anemia results from the destruction of red blood cells and bone marrow suppression. The prevalence of canine ehrlichiosis correlates with the density of tick vectors and can be exacerbated by environmental factors. Canine anemia can be classified as either regenerative or non-regenerative. Objective of the study was, investigating the prognostic value of reticulocyte counts in dogs with ehrlichiosis. The study involved 212 dogs screened between February 2023 and March 2024. Risk factors such as age, sex, breed, and season were recorded. Canine ehrlichiosis was diagnosed by finding morula stages in monocytes and neutrophils in thin blood smear examination. The pathogen was confirmed through PCR-based molecular examination. Reticulocyte count was performed through supravital stain new methylene blue (NMB). Reticulocytes contain ribosomal RNA, which is less condensed than in mature erythrocytes. NMB has a high affinity for ribosomal RNA, resulting in a blue coloration of these immature cells. This staining reaction makes reticulocytes clearly distinct compared to mature red blood cells under a microscope, facilitating their identification and quantification. The study found that the haematological parameters of infected dogs were significantly lower than healthy dogs. The mean ±SE values of Hb, TEC, PCV, and corrected reticulocyte were significantly lower (p<0.001) in infected dogs compared to healthy dogs. These findings suggest that significantly lower values of Hb, TEC, PCV, MCV, MCH, MCHC, and corrected reticulocyte indicate anaemia, normocytic, normochromic anaemia, and non-regenerative anaemia. It can be concluded than in canine ehrlichiosis, anemia is one of the most common finding accounting aprox 28% of total diagnosed cases. Accurate anemia characterization is key for diagnosing and treating ehrlichiosis.

Unraveling the complexity: Case reports of drug-induced hemolytic anemia due to ceftriaxone

Abstract: Drug-induced hemolytic anemia (DIHA) is a rare but significant condition characterized by the premature destruction of red blood cells (RBCs) triggered by certain medications. Ceftriaxone, a commonly used antibiotic, has been linked to DIHA, presenting diagnostic challenges due to its diverse clinical manifestations. This study examines three cases of DIHA caused by ceftriaxone therapy at our center. The patients presented with symptoms such as fatigue, jaundice, and dark urine following ceftriaxone therapy. Laboratory tests indicated hemolytic anemia with decreased hemoglobin, elevated lactate dehydrogenase, and positive direct antiglobulin tests. Immunohematological workups confirmed ceftriaxone-induced antibodies targeting RBCs and guided management strategies, including discontinuation of ceftriaxone, supportive therapy, and corticosteroids. Timely diagnosis and collaboration between clinicians and laboratory specialists are crucial for optimal patient outcomes.

Snake Venom : A Bioactive Cocktail and its Therapautic use

From ancient time whenever we face any problem, we came to nature for the solution. Our nature is self renewable, she has solution for every problem, but we have to find the right path to respond more quickly. This review is regarding chemical nature of snake venom and about different life saving drugs extracted from snake venom. Venoms were originated from non poisonous proteins, and with subsequent generations under evolution these proteins become mutated and modified multiple times to develop deadly poison. With every modification venom becomes enriched with new diverse group of compounds. Main constituents of venom is hydrolyses, PLA2, phosphodiesterases, serine proteases and metalloproteases. Snakes use their venom to paralyzed their prey and to digest food, but these components can be used to treat various life threatening disease. Cobra, krait and rattle snakes are most poisionous snakes and their venom contains different enzymes, are classified as neurotoxic, haemotoxic and cytotoxic in nature and these have different impact upon exposure to animal. Neurotoxic venom destroy nervous system, haemotoxic venom leads to the destruction of red blood cells and also interfere with blood clotting factors, whereas cytotoxic venom can cause necrosis and apoptosis. With the discovary of modern techniques, isolation of different proteins and peptides and analysis of their nature are become easier. Most widely used drugs extracted from snake venom are Tirofiban, Eptifibatide, Captopril, enalapril, cobratide and batroxobin ete. The source of tirofiban, captopril, enalapril batroxobin is the venom of different viper species. On the other hand, eptifibatide is extracted from rattle snake and cobratide is from Chinese cobra .

Correlation Between Red Cell Distribution Width (RDW) and Sequential Organ Failure Assessment (SOFA) Score in Sepsis Patients

Background: There are an estimated 31.5 million cases of sepsis per year, and approximately 61% end up in sepsis shock, with a potential mortality rate of 5.3 million per year. In addition to the sequential organ failure assessment (SOFA) score, several biomarkers have been used to assess severity and predict mortality, including red cell distribution width (RDW). RDW is increased in conditions of ineffective red blood cell production or destruction that occur in inflammation or infection. RDW above 15.5% is associated with rigid and indestructible red blood cells, which can impede microcirculation and contribute to organ dysfunction, a part of the SOFA score.Objective: The aim of this study was to determine the correlation between RDW and SOFA score in sepsis patients admitted to the intensive care unit (ICU) of Rumah Sakit Umum Pusat Haji Adam Malik Medan.Methods: This study used a cohort-prospective study design with a consecutive sampling technique of the population that met the inclusion criteria. The samples were sepsis patients who were admitted to the ICU of Rumah Sakit Umum Pusat Haji Adam Malik Medan in April–June 2023. The data was analyzed by a Pearson or Spearman analysis test.Result: There was a significant correlation between RDW and SOFA score (r = 0.471; p<0.05) in ICU sepsis patients. There was a significant correlation (p = 0.003) between RDW values and SOFA scores on the third day, where there was a moderate degree of correlation (r = 0.471), but there was no significant correlation (p = 0.103) between RDW values and SOFA scores on the first day. The sensitivity, specificity, and cut-off values of RDW were found to be 76.5%, 75%, and 14.75%, which compared to SOFA were 76.5%, 75%, and 10.5.Conclusion: There is a statistically significant relationship between RDW and SOFA, with a moderate correlation.

Zinc Oxide/Carbon Material-Embedded Supramolecular Drug Delivery System with Photoswitching Properties for Highly Selective and Effective Chemotherapy.

Phototherapy has become a hopeful procedure for the treatment of cancer. Nevertheless, the straightforward creation of a theranostic system that can achieve both tumor localization and production of oxygen species is greatly desired yet remains a challenging endeavor. In this study, we synthesized spherical nanostructures by decorating zinc oxide (ZnO) with peanut shell-based carbon (PNS-C) in an aqueous solution. The PNS-C-decorated ZnO (ZnO/PNS-C)-embedded supramolecular system exhibited spontaneous self-assembly. The nanogels that are produced have several desirable characteristics, including exceptional resistance to degradation by light, highly stable nanostructures that form spontaneously in biological environments, outstanding ability to prevent the destruction of red blood cells, and a high level of sensitivity to changes in pH and light. Under light irradiation, the addition of ZnO/PNS-C-incorporated supramolecular provided high reactive oxygen species production. Moreover, in vitro cellular assays demonstrated ZnO/PNS-C-incorporated supramolecular exhibited highly selective and induced phototoxicity into cancer cells and no effect on the viability of normal cells both before and after irradiation. Overall, the ZnO/PNS-C-incorporated supramolecular system has the potential to stimulate advancements in phototherapy by utilizing highly tumor-selective therapeutic molecules. This can lead to a more effective targeted therapy for cancers.

Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion.

A genome-wide association study of alloimmunization in the TOPMed OMG-SCD cohort identifies a locus on chromosome 12.

Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. We performed a genome-wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) cohort, which is part of Trans-Omics for Precision Medicine (TOPMed), with whole-genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. We identified one genome-wide significant locus on chr12 (p = 3.1e-9) with no evidence of genomic inflation (lambda = 1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA-Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.

Transfusion support and pre-transfusion testing in autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is characterized by an increased destruction of red blood cells due to immune dysfunction and auto-antibody production. Clinical manifestations are mainly related to anaemia, which can become life-threatening in case of acute haemolysis. Aiming at counterbalancing severe anaemia, supportive treatments for these patients frequently include transfusions. Unfortunately, free serum auto-antibodies greatly interfere in pre-transfusion testing, and the identification of compatible red blood cell units for AIHA patients can be challenging or even impossible. Problems faced in pre-transfusion testing often lead to delay or abandonment of transfusions for AIHA patients. In this review, we discuss publications concerning global transfusion management in AIHA, with a focus on pre-transfusion testing, and practical clues to manage the selection of transfusion units for these patients. Depending on the degree of transfusion emergency, we propose an algorithm for the selection and laboratory testing of units to be transfused to AIHA patients.

Clinical Exome Sequencing Reveals Novel Mutations in SPTB Gene Associated with Hereditary Spherocytosis in Patients with Suspected Congenital Hemolytic Anemia

Congenital hemolytic anemia (CHA) is defined as the premature destruction of red blood cells (RBC) due to congenital or acquired defects. The hereditary form of hemolytic anemia can be divided into hemoglobinopathies, membranopathies, and enzymopathies. Hereditary spherocytosis (HS) is the most common inherited RBC membranopathy leading to congenital hemolytic anemia. To date; five genes have been associated with HS coding for cytoskeleton and transmembrane proteins, those genes are SPTB, SLC4A1, EPB42, ANK1, and SPTA1. Due to genetic heterogeneity, clinical exome sequencing (CES) was performed on four unrelated Moroccan patients referred for CHA investigation. Sanger sequencing and qPCR were performed to confirm CES results and to study the de novo character of identified variants. The molecular analysis revealed 3 novel mutations and one previously reported pathogenic variant of the SPTB gene confirming the diagnosis of HS in the four patients. Hereditary spherocytosis anemia is a genetically heterogenous disease which could be misdiagnosed clinically. The introduction of novel sequencing technologies can facilitate accurate genetic diagnosis, allowing an adapted care of the patient and his family.

Identification of Babesia Parasite in Ruminants in District Dera Ismail Khan

Background: Babesiosis, a significant tick-borne disease, poses a growing threat to small ruminants and public health due to the pathogenic Babesia parasite. This study focuses on the prevalence of Babesia in cows within the district of Dera Ismail Khan and its impact on red blood cells. Objective: The primary objective of this research was to detect the presence of the Babesia parasite in cows and assess its effects on red blood cells. Methods: Fifty blood samples were randomly collected from cows in Dera Ismail Khan. These samples underwent Giemsa staining and were subsequently examined under a light microscope to identify the presence of the Babesia parasite. Results: Of the 50 blood samples analyzed, only 5 (10%) tested positive for Babesia. This suggests a lower prevalence of babesiosis in the region. The parasite was observed to cause significant destruction of red blood cells. Conclusion: Although babesiosis is not widely prevalent in Dera Ismail Khan, its impact on infected cows is severe, leading to the destruction of red blood cells. Effective monitoring and control measures are essential to mitigate its spread and impact.

Preparation and Characterization of Ferulic Acid Hydrogel and Its Application as a Local Drug Delivery Agent in Periodontitis.

Introduction Periodontitis, a persistent inflammatory condition, impacts the tissues supporting teeth. Beyond mechanically eradicating the biofilm, additional host-modulating agents can aid in the treatment of periodontitis. Among these, gels are a very popular choice for use in the field of dentistry as these systems boast high biocompatibility and bioadhesiveness. These qualities make them easily administered and fabricated. They aretypically placed into the periodontal site via wide-port needle syringes. Many investigations have demonstrated that hydrogels possess the ability for controlled drug release and aid in periodontal wound healing. Hence, this study aimed to develop a ferulic acid hydrogel and assess its effectiveness for managing periodontitis. Materials and methods Ferulic acid hydrogel was prepared followed by haemolysis assay and biocompatibility assay. After the in vitro analysis, a clinical trial was conducted: 20 patients were divided into Group A (comprising patients in whom scaling and root planing (SRP) was done) and Group B (comprising patients in whom SRP along with hydrogel application was done). Each patient's pocket depth (PD), clinical attachment loss (CAL), gingival index (GI), and plaque index (PI) were recorded at baseline and at three months. Intergroup and intragroup comparisons of the parameters were made. Results Ferulic acid hydrogels exhibit a minimal ratio of red blood cell destruction, indicating their low haemolytic activity. Beyond 94 hours, ferulic acid hydrogel demonstrates minimal toxicity towards human fibroblasts, suggesting it has good biocompatibility. When clinical parameters were compared after three months of treatment with SRP alone, significant reductions were observed in all parameters. However, when hydrogel application was done along with SRP, greater reduction was seen in terms of all clinical parameters indicating the efficacy of the ferulic acid hydrogel as an adjunct. Conclusion Ferulic acid has distinct haemolytic activity as well as good biocompatibility. Its use also led to a considerable reduction in all clinical parameters, necessitating its role as a local drug delivery agent in the treatment of periodontitis.

Plain language summary: treatment of paroxysmal nocturnal hemoglobinuria with pegcetacoplan for 48 weeks (PEGASUS study)

What is this summary about? Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, serious blood disease, characterized by uncontrolled activation of the complement system that causes hemolysis (destruction of red blood cells). The complement component 5 (C5) inhibitor eculizumab was the first approved treatment for PNH. The PEGASUS trial compared eculizumab with pegcetacoplan, a new complement component 3 (C3) inhibitor. Because C3 is activated before C5, blocking C3 would also block C5; thus, a C3 inhibitor might prevent hemolysis more completely than a C5 inhibitor in patients with PNH. During the first 16 weeks of PEGASUS, patients received either pegcetacoplan or eculizumab; results were published separately. This summary describes results of the following 32 weeks of PEGASUS, during which all patients received pegcetacoplan to evaluate if pegcetacoplan continued to be effective and safe for up to 48 weeks. What were the results? Pegcetacoplan continued to be effective in participants who received it throughout the study and improved symptoms in participants who switched from eculizumab. The most common adverse events (side effects) were skin irritation at the injection site, hemolysis, nasopharyngitis (runny nose and sore throat), and diarrhea. Adverse events were serious and related to pegcetacoplan in 4 of 77 (5%) patients; all patients recovered from these events. What do the results mean? Pegcetacoplan improved symptoms and was well tolerated for up to 48 weeks by most patients in PEGASUS, suggesting that adult patients with PNH may benefit from long-term pegcetacoplan treatment.

β-Thalassemia gene editing therapy: Advancements and difficulties.

β-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of β-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent β-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of β-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of β-thalassemia diseases.