Good Manufacturing Research Articles

Galenic Laboratory: State of the Art-A Scientific and Technological Discipline, Innovation and Management

The term galenic imply a scientific and technical matter but also an art. Related the hospital practice the future of pharmacy pass though the innovation of the galenic lab. Observing the today hospital practice HP in many countries and the international literature involved it is clear how clinical pharmacy is linked to the galenic lab practice LP. Today more than recent past due to the various kinds of magistral formula requested by the clinicians It is necessary that the clinical pharmacist CP perspective must to be added to the classic galenic lab competencies: this make possible to complete the profile of efficacy and safety of this fundamental and crucial Drugs like the magistral formula and officinal and their use. Aim of this ancient discipline and art is today to provide efficacy and safe drugs for the need of single patient when it is not possible to use the industrial product. The clinical galenic activity can be divided into sterile and non-sterile. (Total parenteral nutrition TPN bags, Pain therapy, oncological parenteral drugs lab UFA, radio drugs and diagnostics and non-sterile galenics).Aim of this work is to deeply investigate this relevant link (Clinical Pharmacy CP with Lab Practice LP) in order to get the really best clinical results for the patients and healthcare org need. Clinical pharmacy CP principle, Pharmaceutical care PC, the managerial competencies and personalized pharmacy added to the best knowledge and competencies in the galenic lab. Make the difference in order to obtain the right final clinical results. The same in this work are submitted to the international pharmacy practitioner, directors, researcher or students the Normative rules operating in an advanced country like Italy: the simplified NBP (NORME DI BUONA PREPARAZIONE), example that can be applied also in the non-advanced nations. In Italy pharmacist can follow or the full NBP (NORME DI BUONA PREPARAZIONE) rules of the official pharmacopeia or the simplified according DM Salute 18.nov.2003. (Related the kind of galenic formula prepared if sterile or not). The NBP (NORME DI BUONA PREPARAZIONE) (good manufacturing rules) introduce a QUALITY CQ SYSTEM MANAGEMENT. The full NBP (NORME DI BUONA PREPARAZIONE) are more used in more complex labs in ex. involved in specialist products (Like oncologic or radio drugs, sterile colliria and other). These rules guarantee the quality, security and the efficacy of a drug prepared in galenic lab. These are based on the responsibility principles, plan, and documentation of all activity. (QUALITY SYSTEM OF INSURANCE CQ). All the phases of the preparation are under the responsibility of the pharmacist. The final quality of the products depends on the correct use of API and excipients, on the right calculations operation, right volume measure or weight operation and the Check on the final products: -following of the procedure, aspects, pakaging and closing system and other request by ITALIAN FU related the specific pharmaceutical form. According NBP (NORME DI BUONA PREPARAZIONE) the lab. Must to be separated (or it must to be separable) form the rest of pharmacy and a second pharmacist (that is different form the pharmacist that prepare) must to check the final preparation. The locals must to be according strictly environmental condition required normative rules by to make possible to prepare in safety way drugs. And it is mandatory to follow the written procedure: instrument verify, training of the pharmacists Cleaning procedure, significations. For Raw materials: it is needed to have certifications, technical sheet, safety sheet, data of the first use, expiry data Working sheet is mandatory to testify the operations. The pharmacist can follow this 2 option related the kind of drugs produced and the characteristic of the lab. It is not the main focus of this work to produce a literal translation of the DM 18/nov /2003 only to submit its general meanings. This can be considered for the authors useful to be added also to the normative rules in force in other non-advanced countries. In order to make more interesting this book some useful concepts of physiology of the stomach and GI tract are reported. The same relevant pharmaceutical concepts and technique with a focus on the capsules CPS as pharmaceutical form (gastro resistance, delayed release), some oral suspension, gels and other few preparation. This work is produced whit a non-conventional approach: it is not a book of pharmaceutical technique. Innovation and management of the system make possible to increase the power of the galenic laboratories In the hospital or in private pharmacy. This work is produced only for international purpose.

Grau de cumprimento das boas práticas de fabricação e perfil microbiológico de linguiças frescas mistas

Abstract Good manufacturing practices in production facilities are necessary to control microbiological growth and prevent foodborne illnesses. Among the various foods that can be contaminated by intensive handling, meat products such as fresh sausages stand out. With this in mind, the aim of this study was to establish a microbiological profile of the fresh sausages produced in the municipality of Alegrete-RS, Brazil, as part of the SIM/SISBI inspection between 2014 and 2016 and to promote and evaluate the producing establishments in terms of compliance with good manufacturing practices. Samples were regularly taken from 10 businesses in the city and tested for thermotolerant coliform bacteria, sulphitereducing Clostridium, coagulase-positive Staphylococcus and Salmonella spp. In addition, the adequacy of good manufacturing practices was assessed and measures in the form of questionnaires, guidelines and training to improve the production chain were implemented in these companies. Over the years, significant improvements in compliance with good manufacturing practices have been observed in the production units. The microbial count of thermotolerant coliforms, sulphite-reducing Clostridium, coagulase-positive Staphylococcus and Salmonella spp. decreased significantly, indicating that the interventions contributed to improving the microbiological profile of the fresh sausage produced in the community.

REGULATORY LANDSCAPE OF UNANI PRODUCTS UNDER D&C ACT AND RULES

The Unani System of Medicine (USM), deeply rooted in tradition, undergoes scrutiny in India under the Drugs and Cosmetics Act (D&C Act) for consumer safety. Regulated by the Central Drugs Standard Control Organization (CDSCO) and guided by the Ayurvedic, Siddha, and Unani (ASU) Drugs Technical Advisory Board, this framework ensures Unani product safety, efficacy, and quality. Manufacturers must comply with Good Manufacturing Practices (GMP), and the D&C Act establishes standards for labeling, packaging, and quality control—essential for marketing Unani products in India. The paper aims to analyze key D&C Act provisions related to Unani formulations, focusing on regulatory procedures. The study sheds light on specific requirements governing Unani drug import, manufacture, distribution, and sale, offering valuable insights into the regulatory framework. It systematically examines the D&C Act, emphasizing sections related to Unani products. Unani Drugs must adhere to prescriptions in the 14 recognized Unani texts (Schedule I of D&C Act). The Drugs and Cosmetics Rules of 1945 cover Unani Medicine in Parts 16 to 19, addressing licensing (Part 16), testing (Part 16A), labeling and packaging (Part 17), and quality control standards (Part 19). In conclusion, this paper provides a nuanced analysis of the regulatory landscape governing Unani products under the Drugs and Cosmetics Act. It elucidates legal intricacies, emphasizing challenges in compliance, standardization, and merging traditional knowledge with contemporary requisites. The insights contribute to understanding the regulatory environment surrounding Unani medicines, balancing cultural heritage preservation with ensuring efficacy and safety for consumers.

Good manufacturing practice inspections conducted by Tanzania medicines and medical devices authority: a comparative study of two fiscal years from 2018 to 2020.

Good Manufacturing Practices (GMP) is the bedrock of quality assurance in the pharmaceutical industry that ensures that products are consistently produced and controlled according to quality standards. This study compared the GMP conformance of pharmaceutical facilities across two fiscal years, 2018/2019 and 2019/2020, using the East African GMP Compendium on Good Manufacturing Practices, 2014, as a benchmark. We analyzed the proportion of conformance of foreign pharmaceutical industries to GMP standards and reported the aggregated data over a two-year period. Inspected facilities had notable non-conformances, most commonly related to laboratory quality control and premises. We noted a downward trend in conformance in 2019/2020 compared with 2018/2019, with only 32.9% of facilities adhering to EAC GMP requirements, down from 50% in the previous year. The COVID-19 pandemic has affected the ability to conduct on-site inspections, and may have contributed to the lower conformance rate. These findings underscore the crucial need to continue GMP inspections and the importance of taking corrective actions to ensure adherence to the quality standards for products marketed in Tanzania. The study further revealed the significance of desk reviews in assisting regulatory authorities in facing unforeseen challenges such as pandemics.

Toward microfluidic continuous-flow and intelligent downstream processing of biopharmaceuticals.

Biopharmaceuticals have emerged as powerful therapeutic agents, revolutionizing the treatment landscape for various diseases, including cancer, infectious diseases, autoimmune and genetic disorders. These biotherapeutics pave the way for precision medicine with their unique and targeted capabilities. The production of high-quality biologics entails intricate manufacturing processes, including cell culture, fermentation, purification, and formulation, necessitating specialized facilities and expertise. These complex processes are subject to rigorous regulatory oversight to evaluate the safety, efficacy, and quality of biotherapeutics prior to clinical approval. Consequently, these drugs undergo extensive purification unit operations to achieve high purity by effectively removing impurities and contaminants. The field of personalized precision medicine necessitates the development of novel and highly efficient technologies. Microfluidic technology addresses unmet needs by enabling precise and compact separation, allowing rapid, integrated and continuous purification modules. Moreover, the integration of intelligent biomanufacturing systems with miniaturized devices presents an opportunity to significantly enhance the robustness of complex downstream processing of biopharmaceuticals, with the benefits of automation and advanced control. This allows seamless data exchange, real-time monitoring, and synchronization of purification steps, leading to improved process efficiency, data management, and decision-making. Integrating autonomous systems into biopharmaceutical purification ensures adherence to regulatory standards, such as good manufacturing practice (GMP), positioning the industry to effectively address emerging market demands for personalized precision nano-medicines. This perspective review will emphasize on the significance, challenges, and prospects associated with the adoption of continuous, integrated, and intelligent methodologies in small-scale downstream processing for various types of biologics. By utilizing microfluidic technology and intelligent systems, purification processes can be enhanced for increased efficiency, cost-effectiveness, and regulatory compliance, shaping the future of biopharmaceutical production and enabling the development of personalized and targeted therapies.

Advances in High-Performance Liquid Chromatography (HPLC) Method Development and Validation: A Comprehensive Review

High-Performance Liquid Chromatography (HPLC) stands as the cornerstone technique for the detection, separation, and quantification of drugs in various matrices. Method optimization necessitates a thorough investigation of multiple chromatographic parameters, encompassing sample pretreatment, mobile phase composition, column selection, and detector configuration. This article aims to comprehensively address the processes of method development, optimization, and validation within the realm of HPLC. The inherent advantages of HPLC, including its rapidity, specificity, accuracy, precision, and automation feasibility, render it an indispensable tool for analyzing a wide spectrum of drugs in complex multi-component dosage forms. Furthermore, HPLC method development and validation hold paramount importance across the spectrum of drug discovery, development, and manufacturing, as well as in diverse human and animal studies. The validation of analytical methods during drug development and manufacturing is imperative to ensure their fitness for the intended purpose. Adhering to Good Manufacturing Practice (GMP) requirements, pharmaceutical industries must establish comprehensive validation policies outlining the validation procedures. This article primarily delves into the optimization of HPLC conditions, emphasizing the critical role of method refinement in ensuring robust and reliable analytical methods.

Standardized GMP-Compliant Scalable 3D-Bioprocessing of Epidermal Stem Cells for Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) pose a significant threat to the health and well-being of individuals with diabetes, often leading to lower limb amputations. Fortunately, epidermal stem cell therapy offers hope for improving the treatment of DFUs. By leveraging 3D culture techniques, the scalability of stem cell manufacturing can be greatly enhanced. In particular, using bioactive materials and scaffolds can promote the healing potential of cells, enhance their proliferation, and facilitate their survival. Furthermore, 3D tissue-mimicking cultures can accurately replicate the complex interactions between cells and extracellular matrix, thereby ensuring that the stem cells are primed for therapeutic application. To ensure the safety and quality of these stem cells, it is essential to adhere to good manufacturing practice (GMP) principles during cultivation. This chapter provides a comprehensive overview of the step-by-step process for GMP-based 3D epidermal stem cell cultivation, thus laying the groundwork for developing reliable regenerative medicine therapies.

HUBUNGAN RIWAYAT KERJA TERHADAP PENGETAHUAN VALIDASI DAN KUALIFIKASI BERDASARKAN CPOTB DI USAHA KECIL OBAT TRADISIONAL PT. X di DAERAH ISTIMEWA YOGYAKARTA

Validation and qualification are important activities the pharmaceutical industry to produce quality and safe drugs. Good Manufacturing Practices for Traditional Medicines (CPOTB) is a guideline for the traditional medicine industry to produce medicines with guaranteed quality from validation and qualifications. Employee knowledge in carrying out validation and qualifications in the traditional medicine industry is very necessary to support the production quality assurance process. The aim of the research is to determine the relationship between work history (length of work and work area) on validation knowledge and qualifications based on CPOTB in the small business of traditional medicine PT. X in the Special Region of Yogyakarta. The type of research is descriptive quantitative with a cross sectional method. The research uses primary data from questionnaires of 35 employees who work in the production sector of PT. X. The results showed that there was no work history relationship with employee knowledge of CPOTB, with a p-value of 0.496 (<0.05) in the length of work and a p-value of 0.724 (<0.05) in the work area. From the data it can be concluded that the length of work and employee work area in the production sector are not related to employee knowledge of CPOTB.

Platelet-Rich Plasma as Xenofree-Growth Factor For Mesenchymal Stem Cells Culture

Stem cell-based therapy is currently believed to be the future of medicine. The type of stem cell that is widely used in cell-based therapy is mesenchymal stem cells (MSCs). In stem cell-based therapy, the MSCs that will be used mostly need to be expanded first by culturing the cells. The serum that is often used in MSCs culturing is a fetal bovine serum (FBS). However, animal components should be avoided in clinical applications and Good Manufacturing Practices (GMP). FBS is not adhering to GMP, which compromises the safety and effectiveness of cell-based therapies. Therefore, other supplements are required for cultures without animal serum constituents. Platelet-rich plasma (PRP) is a plasma fraction derived from blood with a platelet concentration of 3-5 times higher than in blood. Several studies have shown that PRP contains various growth factors that can increase the proliferative and differentiation capacity of MSCs which is equivalent to or even better than FBS. PRP also has the advantage that it can be an autologous or allogeneic product from human peripheral blood, so it is free from animal substances. Therefore in the future PRP has great potential as an alternative to FBS both in culture expansion and in MSCs processing.

Prevalence of Common Microbiological Pathogen Contamination in Processed Milk and Milk Products in Nairobi County, Kenya

Milk has an outstanding nutritional quality but it is also an excellent medium for bacterial growth and an important source of bacterial infection when consumed without pasteurization. This study aimed at establishing the prevalence of Total Viable Count (TVC), Escherichia coli, Staphylococcus aureus and Listeria monocytogenes contamination on processed milk and milk products. The study was carried out in Karen, Kibera and Langata Sub- Counties of Nairobi County which were purposively chosen because they have glaring contrasts in living standards. Samples of fresh milk, yoghurt cheese and ice creams were collected from supermarkets and prepared for analysis of microorganisms. All isolates were characterized and identified based on their morphological and cultural characteristics. TVC were detected in 100% of the samples collected and there was significant statistical variation (P ≤ 0.05) in the contamination level among the products. Of the samples collected in Karen, ice cream had the highest contamination level (3.26 log10 CFU ml-1). Ice cream samples from Langata had the highest TVC contamination levels at 4.35 log10 CFU ml-1. The overall prevalence of E. coli in milk and milk products was 41.6% with a mean count of 0.34 log10 CFU ml-1 in Karen, 0.07 log 10 CFU ml -1 in Kibera and 0.11 log 10 CFU ml -1 in Langata while Staphylococcus aureus was detected in 33.3% of the milk and milk products. The occurrence and detection of E. coli and S. aureus foodborne pathogens in milk and milk products represent a health risk to consumers. Therefore, there is need to improve the microbial quality of milk and milk products by employing measures that will establish proper management practices to ensure improved hygiene, good manufacturing practices and food systems that will help to minimize microbial contamination.

Implementation of Good Manufacturing Practices in Milk Processing Companies in Nairobi County and Microbial Contamination of Milk and Milk Products

Good manufacturing practice involves a series of measures to be adopted by the food industries in order to guarantee the safety and conformity of food products to specific regulations. Even though good manufacturing practices are vital systems in food safety and is associated with minimum sanitary and processing requirements for the food industry, only a few studies have reported GMP implementation by small milk processing companies. Therefore, the present study was undertaken in milk processing firms to evaluate the implementation of good manufacturing practices for control of microbial contamination in milk and milk products. Purposive, random and stratified sampling techniques was used to identify milk processing companies. Ten processing facilities were purposively sampled for the study. The representatives were interviewed, using a pretested questionnaire and data was collected and analyzed. All the processors had qualified personnel handling milk and milk products with a daily processing capacity of 20000-30000 litres. It was observed that the processors complied with all regulatory and licensing requirements and had in place critical process controls with majority indicating pasteurization at temperatures ranging from 80-90oC as the most common method. The processors had several food safety management systems such as ISO 22000, GMPs, and HACCP which were handled by trained and competent staff. It was observed that all the processors tested for total viable counts (TVC), and E. coli while only 50% and 33.3% of the processors tested for S. aureus and L. monocytogenes respectively. Furthermore, the processors (33.3%) reported E. coli as the main contaminant while L. monocytogenes were not detected. A majority (83.3%) had well-documented cleaning programs and had a system of controlling cross contamination which was enforced through different colour codes (66.7%), memos and notices (16.7%) and through colour coding of processing equipment (16.7%). In conclusion, the present study discovered that milk processors had implemented good manufacturing practices (GMP) and conformed to good processing practices.

Foodborne Diseases: A Study before and during the COVID-19 Pandemic in Brazil.

Foodborne Diseases (FBDs) are a worldwide problem and occur after contaminated food has been ingested, signaling a lack of food quality. Even though the SARS-CoV-2 virus is not transmitted through food, the COVID-19 pandemic has caused several challenges worldwide that have had direct implications on food production and handling, stimulating and reinforcing the adoption of good manufacturing and food handling practices. The aim of this study was to analyze data on notifications of FBD in Brazil in the years before (2018 and 2019) and during (2020 and 2021) the COVID-19 pandemic. Secondary data from the National System of Notifiable Diseases was analyzed, evaluating: overall incidence rate, lethality and mortality, contamination sites, and criteria for confirming the etiological agent. There were 2206 records of FBDs, and the mortality rate was 0.5% in both periods. The incidence rate before the pandemic was 6.48 and during the pandemic was 3.92, while the mortality coefficient was 0.033 before and 0.019 during the pandemic, both per 100,000 inhabitants. There was no significant difference in the number of FBD notifications in the evaluated periods. There was a migration of the location of FBD, with a significant increase in FBD notifications in hospitals and health units and a reduction in notifications from social events. There was a significant increase in the type of criteria used to confirm outbreaks, with an increase in clinical laboratory tests and clinical reports for bromatology. The increase in notifications in hospitals and health units demonstrates the necessity of improving food safety knowledge and the attitudes and practices of food handlers and healthcare professionals.

ETİBARLI İSTEHSALAT TƏCRÜBƏSİNƏ DAİR XÜSUSİ TƏLƏBLƏRİN HAZIRLANMASININ ZƏRURİLİYİ

The article investigates existing international and regional requirements on various areas of Good Manufacturing Practice for the production of medicinal products, emphasizes the im-portance of preparing national requirements - annexes to the basic requirements of Good Manu-facturing Practice in the mentioned area, and gives relevant proposals on the relevant topic.

Safety Assessment of Hops as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Humulus Lupulus (Hops) Extract (reported functions include antimicrobial agent and hair conditioning agent) and Humulus Lupulus (Hops) Oil (reported function is fragrance). The Panel reviewed the relevant data related to these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. For these ingredients, the Panel was concerned about the presence of 8-prenylnaringenin, β-myrcene, and quercetin in cosmetics, which could result in estrogenic effects, dermal irritation, and genotoxicity, respectively. Industry should use current good manufacturing practices to limit impurities and constituents of concern. The Panel concluded that Humulus Lupulus (Hops) Extract and Humulus Lupulus (Hops) Oil are safe in cosmetics in the present practices of use and concentration when formulated to be non-sensitizing.

Strategi Peningkatan Mutu dan Keamanan Produk Olahan Melalui Pelatihan Good Manufacturing Practice (GMP) pada UKM Piyasan Nanggroe Kabupaten Aceh Utara

Community Engagement activities were conducted in Gampong Matang Meunye, Aceh Utara District, with a focus on the development of Micro, Small, and Medium Enterprises (MSMEs) represented by the UKM Piyasan Nanggroe group. This group possesses expertise in producing high-quality dried bananas, referred to as "pisang gintong," and aspires to scale up production extensively. The objective of this Community Engagement was to provide support in enhancing production and business legality, particularly in the realm of business management, encompassing business motivation, financial recording, and digital marketing. Furthermore, this endeavor aimed to elevate product quality by implementing Good Manufacturing Practices (GMP) with hygienic and efficient standards and introducing processed banana products using state-of-the-art processing technology that is more hygienic and healthier while leveraging local resources. The implementation of the activities comprised three stages: preparation, program execution, and evaluation. The preparation phase encompassed pre-surveys, team formation, proposal development and submission, team and partner coordination, and the preparation of training materials. The program execution stage involved disseminating information and conducting discussions to impart knowledge in business management, digital marketing, and GMP practices. The evaluation and reporting phase ensured the success of the program. After the program, it is anticipated that MSME entrepreneurs within the UKM Piyasan Nanggroe group will experience increased production capacity, a better understanding of the importance of sound financial record-keeping, the implementation of marketing strategies through labels (Halal and branding), and the adoption of hygienic standard processing technology. This article aims to provide practical guidance for MSME entrepreneurs in enhancing their quality and competitiveness.

Penerapan Sistem Good Manufacturing Practices (GMP) Pada Proses Pembekuan Ikan Layur DI CV. Sinar Harapan Berau

The freezing industry requires a basic eligibility program to provide guarantees for a food safety system. The application of GMP or Good Manufacturing Practices in the food industry is a requirement to produce products that are safe for consumption. The aim of the study was to examine the application of GMP in freezing layur fish at CV. Sinar Harapan Berau and identify non-compliance factors in the implementation of GMP. The results showed that the application of GMP in CV. Sinar Harapan Berau has largely complied with the CPPOB guideline requirements. Based on the analysis of non-conformity, there are 14 aspects that are suitable and 4 aspects that are not suitable with the percentages of 77.8% and 22.2%, respectively. Several factors cause non-compliance with GMP, namely puddles of water on the road leading to the production site, the road has not been cemented, and without laying stones. There are no washing facilities in the toilet area, there is still rust on the tables and pans in the production area. CV. Sinar Harapan also does not yet have laboratory facilities for quality control and safety of raw materials, but only inspects organoleptically.

Development of a Rapid Adeno-Associated Virus (AAV) Identity Testing Platform through Comprehensive Intact Mass Analysis of Full-Length AAV Capsid Proteins.

Adeno-associated viruses (AAVs) are commonly used as vectors for the delivery of gene therapy targets. Characterization of AAV capsid proteins (VPs) and their post-translational modifications (PTMs) have become a critical attribute monitored to evaluate product quality. Liquid chromatography-mass spectrometry (LC-MS) analysis of intact AAV VPs provides both quick and reliable serotype identification as well as proteoform information on each VP. Incorporating these analytical strategies into rapid good manufacturing practice (GMP)-compliant workflows containing robust, but simplified, data processing methods is necessary to ensure effective product quality control (QC) during production. Here, we present a GMP-compliant LC-MS workflow for the rapid identification and in-depth characterization of AAVs. Hydrophilic interaction liquid chromatography (HILIC) MS with difluoroacetic acid as a mobile phase modifier is utilized to achieve the intact separation and identification of AAV VPs and their potential proteoforms. Peptide mapping is performed to confirm PTMs identified during intact VP analysis and for in-depth PTM characterization. The intact separations platform is then incorporated into a data processing workflow developed using GMP-compliant software capable of rapid AAV serotype identification and, if desired, specific serotype PTM monitoring and characterization. Such a platform provides product QC capabilities that are easily accessible in a regulatory setting.

Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor.

AZD4747 is a KRASG12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [11C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [11C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory hepatic disorder with no effective treatment. Mesenchymal stromal cells (MSCs) have emerged as a promising treatment owing to their unique advantages. However, their heterogeneity is hampering use in clinical applications.MethodsWharton’s jelly derived MSCs (WJ-MSCs) were isolated from 58 human donors using current good manufacturing practice conditions. Gene expression profiles of the WJ-MSCs were analyzed by transcriptome and single-cell RNA-sequencing (scRNA-seq), and subsequent functional differences were assessed. Expression levels of programmed death-ligand 1 (PD-L1) were used as an indicator to screen WJ-MSCs with varied immunomodulation activities and assessed their corresponding therapeutic effects in a mouse model of concanavalin A-induced autoimmune hepatitis.ResultsThe 58 different donor-derived WJ-MSCs were grouped into six gene expression profile clusters. The gene in different clusters displayed obvious variations in cell proliferation, differentiation bias, trophic factor secretion, and immunoregulation. Data of scRNA-seq revealed four distinct WJ-MSCs subpopulations. Notably, the different immunosuppression capacities of WJ-MSCs were positively correlated with PD-L1 expression. WJ-MSCs with high expression of PD-L1 were therapeutically superior to WJ-MSCs with low PD-L1 expression in treating autoimmune hepatitis.ConclusionPD-L1 expression levels of WJ-MSCs could be regarded as an indicator to choose optimal MSCs for treating autoimmune disease. These findings provided novel insights into the quality control of MSCs and will inform improvements in the therapeutic benefits of MSCs.

Pendampingan Dan Penguatan Daycare Malnutrition Sebagai Upaya Penurunan Stunting Di Wilayah Kerja Puskesmas Sekaran

Malnutrition is a health problem that is still often found in developing countries. Based on SSGI data for 2022, the prevalence of stunting in Semarang City reached 10.4%. The Sekaran Community Health Center area recorded 3.07% of stunted toddlers in 2022, while as of December 2022 there were 74 underweight toddlers and 40 wasted toddlers. The establishment of daycare is one of the efforts made by the Sekaran Community Health Center to overcome the problem of stunting. This community service aims to assist nutritional care for toddlers with stunting at the Sekar Kasih Daycare located in Patemon Village, with the implementation of community service activities taking place since the daycare was established on March 1 2023 - August 1 2023. The programs offered and implemented include: other things include preparing a 10+1 day menu cycle, anthropometric measurements, GMP (Good Manufacturing Practices) training for 20 people consisting of daycare officers and posyandu cadres, preparing standard operating procedures (SOP) for organizing meals in daycares, and preparing a pocket book on food ingredient specifications. The results of this activity are a 10+1 day menu cycle, an increase in knowledge based on the average score from 89 to 96.5, and SOPs for managing food in daycare.