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Background: Cellular senescence and the senescence-associated secretory phenotype (SASP) are pivotal factors influencing aging and age-related diseases. SASP secretes cytokines, chemokines, metalloproteinases, and growth factors that cause chronic inflammation. C-C ligand 2 (CCL2) and transforming growth factor-beta (TGF-β) are SASP markers secreted by senescent cells. This study investigated the relationship between the FOXO3 variant rs2802292 and SASP markers, focusing on CCL2 and TGF-β. Materials and methods: A cross-sectional study involving 72 elderly individuals from Jakarta was conducted. A sandwich enzyme-linked immunosorbent assay (ELISA)was used to quantify CCL2 and TGF-β concentrations. Random blood glucose, blood pressure, and FOXO3 rs2802292 genotyping data were obtained from a previous study. Differences in CCL2 and TGF-β concentrations between genotype groups were analyzed using one-way ANOVA and the Kruskal-Wallis test. Meanwhile, differences in CCL2 and TGF-β concentrations between allele groups were analyzed using the Mann-Whitney test. Results: The CCL2 and TGF-β concentrations of the subjects were 66.5 (10.58-190.9) pg/mL and 6,319 (2,379-13,846) pg/mL, respectively. There were significant differences in CCL2 concentrations among the FOXO3 rs2802292 genotypes (p=0.041). However, there were no significant differences in TGF-β concentrations among FOXO3 rs2802292 genotypes (p=0.955). Subjects with the G allele had significantly lower CCL2 concentrations compared with those with the T allele (p=0.033). TGF-β concentrations did not significantly differ between G and T alleles (p=0.771). Conclusion: CCL2 concentrations are associated with the FOXO3 variant rs2802292 in the elderly population. The T allele of FOXO3 rs2802292 increased CCL2 concentration and slightly decreased TGF-β concentration in elderly individuals. Keywords: aging, SASP, CCL2, TGF-β, SNP, FOXO3, rs2802292

Background: Hypertensive disorders, particularly preeclampsia, are major contributors to maternal mortality and neonatal morbidity. Angiogenic imbalance plays a critical role in placental ischemia, a hallmark of preeclampsia. Purpose: This study aimed to investigate the roles of endoglin, soluble endoglin (sEndoglin), and matrix metalloproteinase-14 (MMP-14) in the angiogenic imbalance observed in preeclampsia placentas compared to normal-term placentas. Method: A cross-sectional study was conducted using 68 placental samples: 34 from normal-term pregnancies and 34 from preeclampsia cases. Concentrations of endoglin, sEndoglin, and MMP-14 were measured using the sandwich ELISA method, and protein levels were determined using the Christian Warburg method. Data were analyzed using SPSS version 20. Results: The concentration of endoglin in preeclampsia placentas was slightly higher (1.37 [0.2–2.2] ng/μg protein) compared to normal placentas (1.12 [0.6–14.1] ng/μg protein), although the difference was not statistically significant. In contrast, sEndoglin (0.05 [0.0–0.01] ng/μg protein vs. 0.02 [0.0–0.3] ng/μg protein) and MMP-14 (0.14 [0.1–0.6] ng/μg protein vs. 0.11 [0.1–1.3] ng/μg protein) concentrations were significantly higher in preeclampsia placentas compared to normal placentas. All parameters showed a gradual decrease with advancing gestational age. sEndoglin and MMP-14 demonstrated a strong positive correlation (r = 0.658, p < 0.001), while endoglin and MMP-14 exhibited a moderate positive correlation (r = 0.554, p < 0.001). Conclusion: Endoglin, sEndoglin, and MMP-14 were differentially expressed in preeclampsia placentas, with sEndoglin and MMP-14 significantly elevated. These findings highlight their potential role in angiogenic imbalance and may provide insight into the pathophysiology of preeclampsia.

Pro- and anti-inflammatory mediators need to be released in a balanced way to maintain a healthy state as we age. One important regulatory element in the equilibrium of pro- and anti-inflammatory mediators is NF-κB. The purpose of this study was to examine how S. platensis affected the control of inflammatory mediators in young, healthy, emerging adults and adults in rats. In this investigation, 200 mg/kg BW of S. platensis extract was administered to six groups of male Wistar rats, ages 12, 18, and 24 weeks, along with a control group. In both the treatment and control groups, NF-κB p65 protein expression was lower at 24 weeks than it was at 12 and 18 weeks. TNF-α and COX-2 proteins were lower in the treatment group than in the control group. All age groups in the treatment group had higher levels of IL-10 protein than the control group. The quantity of NF-κB p65 was positively correlated with COX-2 and TNF-α. By raising the concentration of NF-κB p65, the ethanolic extract of S. platensis altered a mediator of cellular immunity. A decrease followed this in TNF-α and COX-2 and a rise in IL-10 in the rat spleen at different ages.

Tuberculosis is caused by Mycobacterium tuberculosis infection. During M. tuberculosis infection, there is a decrease in the partial pressure of oxygen in the granuloma microenvironment, which causes the hypoxia-inducible factor (HIF) to become stable. HIF functions as a transcription factor that regulates the expression of genes crucial for metabolic adaptation in hypoxic conditions. Recent research suggests that HIF plays a vital role in infectious and inflammatory conditions. Several studies have demonstrated that HIF signaling can enhance macrophages antimicrobial activity and bactericidal effect against M. tuberculosis, such as increasing macrophage autophagy, enhancing the effects of rifampicin, inhibiting p38 MAPK signaling, enhancing the regulation of effector antimicrobial pathways mediated by human β defensin 2 (hBD2) and vitamin D receptor (VDR), redirecting energy metabolism to glycolysis, and producing various cytokines. All these responses ultimately result in the inhibition of intracellular M. tuberculosis growth. HIF has therapeutic implications, potentially being a new candidate for host-directed therapy as a complement to existing antituberculosis drugs. Understanding the role of HIF in macrophages during M. tuberculosis infection and comprehending the host-pathogen relationship with M. tuberculosis is advantageous for developing future therapies. Keywords: Mycobacterium tuberculosis, macrophages, hypoxia-inducible factor

The immune system operates like an orchestra that harmoniously maintains the homeostasis balance while protecting from external or internal pathogens attack. Inflammation is one of the key critical immune defenses to eradicate pathogens and encourage tissue repair and recovery by activating the host’s immune and non-immune cells. As a part of the immune response during inflammation, blood platelets serve various functions; however, their activation and involvement in inflammation can also contribute to pathological conditions, such as thrombosis, which results in myocardial infarction, stroke, and venous thromboembolism. Activated platelets can mobilize and release intracellular granules (alpha and dense granules), which include secondary mediators like chemokine PF4/CXCL4. In contrast to most other chemokines, PF4 participates in several long-term regulatory processes, such as cell differentiation, survival, and proliferation. However, recent findings suggest that PF4 is also responsible for modulating macrophage polarization, which can substantially impact the development of induced immune thrombotic thrombocytopenia. This review aims to explain how PF4 induced vascular problems by modulation of macrophage development during immunological thrombocytopenia. A literature search using the keywords PF4, CXCL4, macrophage M4, platelet macrophage M4, and induced immune thrombocytopenia was done using the following databases: Google Scholar, ProQuest, ScienceDirect, and Scopus for articles published from 2000 to 2023. The literature study was done to find the connection between platelet activation, macrophage modulation, and vascular problems such as atherosclerosis and thromboembolism in induced immune thrombotic thrombocytopenia. Several recent studies on PF4, macrophage modulation, and vaccine-induced thrombotic thrombocytopenia were carefully reviewed. This review concludes that macrophage polarization modulation is promising in managing vascular problems in patients with induced immune thrombotic thrombocytopenia.

Asthma is a major health problem and one of the leading causes of death in the world. The prevalence of asthma in Indonesia is high, with a recurrence >50%. Allergic sensitization in asthma is mainly caused by house dust mite (HDM) allergens, both from the mite’s body and its contaminants (e.g., lipopolysaccharides). HDM allergens stimulate several pathways in the innate immune response based on the HDM allergen groups that sensitize them. The innate immune response to HDM allergen exposure occurs when pattern recognition receptors (PRRs) recognizes the allergen, thereby stimulating respiratory epithelial cells to release cytokines, namely, thymic stromal lymphopoietin (TSLP), interleukin-25 (IL -25), and IL-33. The release of IL-25 and IL-33 activates group 2 innate lymphoid cells (ILC2) to release Th2-type cytokines (i.e., IL-5 and IL-13), resulting in allergic airway inflammation via IgE secretion by B cells, recruitment of eosinophils, and respiratory tract remodeling. Dendritic cells induce an adaptive immune response through Th2 activation in the sensitization and effector phases. Other mediators that contributed to the innate immune response include C-C motif chemokine ligand 20 (CCL-20) and granulocyte-macrophage colony-stimulating factor (GM-CSF). A deeper understanding of the components and mechanisms involved in innate immunity against HDM allergens creates the potential to develop alternative therapeutic targets for allergic asthma treatment. Keywords: house dust mite allergens, innate immunity, allergic asthma, respiratory epithelium, inflammatory cytokines

Background: Maternal exposure to cigarette smoke during pregnancy and lactation might harmful for the fetus. The smoke contains many free radicals that could be eliminated by antioxidant. This study aimed to investigate the effect of Spirulina platensis ethanol extract as antioxidant against cigarette smoke exposure during pregnancy until lactation by assessing oxidative stress markers in neonatal brain tissues. Methods: The experimental study used 26 offspring divided into four groups: (C) = offspring of maternal control group; (Cg) = offspring of maternal exposed to cigarette smoke; (CgSp) = offspring of maternal given spirulina and exposed to cigarette smoke; and (Sp) = offspring of maternal given spirulina only group, during gestation and 9 days lactation (30 days). Each group consisted of 6 offspring obtained from 2 adult females mated with male Sprague-Dawley rats. The exposure of cigarette smoke was 4 burn cigarettes/day for 30 days. The dose of extract was 200 mg/kg BW. The offspring were sacrificed, and the brain tissues were taken for MDA, MnSOD activity, as well as catalase activity, carbonyl, and GSH. Results: There was no significant differences in MDA level between groups. The carbonyl, SOD, and catalase activity did not differ between the control and smoked group. Conclusion: Exposure of four burned cigarettes smoke per day during pregnancy, and 9 days of lactation did not trigger oxidative stress. However, the effect of Spirulina platensis administration on rat offspring brain could not be analyzed.

Asthma is the most frequent noncommunicable disease and one of the leading causes of years lived with disability. Asthma has a severe impact on a patient's life, being able to disturb the activities of both children and adults. The morbidity and mortality of asthma may depend on the severity and progressiveness of the symptoms experienced by the patient. Different and complex pathomechanisms underline the pathology of asthma, in which the regulation of innate and adaptive immune responses plays a role. There is a complex interaction between immune cells including chemokines involved in the pathogenesis of asthma. Immune cell trafficking is orchestrated by a family of small proteins called chemokines. Leukocytes express cell-surface receptors that bind to chemokines and trigger transendothelial migration. This review article outlines the main role of chemokines in inflammatory reactions that occur in allergic asthma, based on the latest literature studies that have been published previously. The allergic reaction in asthma expresses various chemokines and their receptors. Chemokines including eotaxins (CCL11, CCL24, and CCL26), CCL2, CCL5, CCL17, and CCL22 regulate immune cells that under pathological conditions travel to the inflammatory site, mainly in the lung, to protect the body from pathogen invasion. Chemokines are released by a number of immune cells such as monocytes, dendritic cells, mast cells, and epithelial cells in the airway. The biological effects of chemokine production are enhanced by secreted cytokines when an allergic reaction occurs in asthma, such as IL-4, IL-5, and IL-13. Chemokines cause an accumulation of different inflammatory cells at the site of inflammation, which ultimately results in tissue damage to the airway. The inhibition of the reactions evoked by the interaction between chemokines and their receptors is considered a candidate for the development of potent therapeutic drugs for asthma in the future.

The gastrointestinal (GI) tract represents our most intimate contact with the external environment. The GI tract responsible for extracting the appropriate nutrients we need to thrive, maintaining an appropriate balance of helpful and harmful microbes, and acting as a conduit for waste removal. In essence, the extracellular matrix of gut mucosal biofilm is a complex network of microbes and their secretions, as well as the host's secretions and signals (mainly mucus/mucin). Mucin, bacterial polysaccharides, and protein combine to form a unique mucosal biofilm that serves as a home for a variety of commensal and pathogenic organisms in the host. Maintaining proper mucosal barrier function is vital for both GI and systemic health. The lumen of the gut contains numerous entities that should never reach the bloodstream or lymphatic system. The mucosal barrier's integrity is maintained by a single layer of tightly fitted columnar epithelial, and more than 70% of the immune system components are closely associated with the GI tract.

Background: Preeclampsia is one of the factors causing the high maternal mortality rate. The risk of morbidity and mortality is higher in Early Onset Preeclampsia (EOPE). Failure of spiral artery remodeling can cause oxidative stress that can inhibit placental development and increase trophoblast apoptosis. Objective: This study aims to analyze the oxidative stress and apoptosis of EOPE placentas. Methods: This study is an observational study with a cross-sectional design. A total of 31 EOPE placentas and 31 normal term placentas were used to measure the concentration of malondialdehyde (MDA) and the relative mRNA expression of FOXO3 and CASP3 using the spectrophotometric and RT-qPCR methods. Results: There was no difference in MDA concentration (p = 0.580) and FOXO3 (p = 0.467) and CASP3 (p = 0.243) mRNA expression in the normal and EOPE groups. There was a strong positive correlation between FOXO3 and CASP3 mRNA expression in the normal (p= 0.0001; r = 0.938) and EOPE groups (p = 0.0001; r = 0.855). There was no correlation between MDA concentration to FOXO3 (p = 0.124; r = 0.282) and CASP3 (p = 0.569; r = 0.106) mRNA expression in normal placenta. There was positive correlation between MDA concentration to FOXO3 (p = 0.016; r = 0.429) and CASP3 mRNA expression in EOPE placenta (p = 0.028; r = 0.395). Conclusion: These results indicate that cell integrity is still maintained through the autophagy process and the level of apoptosis in the EOPE placenta is regulated by ROS through FOXO3.

This study examined the hypothesis that there is an impairment of macrophageal function in spinal TB. We examined macrophageal functions in spinal TB patients. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of five spinal TB patients and five healthy persons as control. The isolated monocytes were cultured with stimulation of macrophage colony-stimulating factor (M-CSF) for seven days for maturation. The phagocytic ability of the macrophages derived from monocytes was measured. Also, nitric oxide (NO), myeloperoxidase (MPO), beta-glucuronide, and acid phosphatase activity was investigated. We found that the monocytes collected from patient PBMCs were significantly fewer than those of the control group (2992.103 vs. 6474.103 (cells/mL)). There were also fewer macrophages that had adhered to sheep red blood cells (SRBC) (598.103 vs. 264.103 (cells/mL)). However, NO production (2346 vs. 325.17 (µmol/gram of protein)), and the MPO (570.7 vs. 17.4 (unit/mg), beta-glucuronide (0.149 vs. 0.123 (μmol/hour/100 mg of protein)), and acid phosphatase activities (1776.9 vs. 287.9 (μmol/hour/100 mg of protein)) of the macrophages in the spinal TB group were markedly higher than in the healthy group. Despite the low adhesion to foreign bodies, the intracellular processing of TB macrophages, including oxidative activity and lysosome function, was significantly high. These results suggested the impairment of macrophageal function in spinal TB. Possibly, there is a dominance of innate non-specific immunity in spinal TB infection.

Chitosan-based particles are desirable materials for drug delivery because of their muco-adhesiveness in tissues, biocompatibility, low toxicity and effectiveness in antigen transport. It is still a challenge to prepare chitosan-based particles with high stability and by an effective method. Here we developed chitosan-based nanoparticles for the delivery of toll-like receptor 9 ligands, cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs), which can induce the change from Th-2 type to Th-1 type immune response. Because of the low tolerance to DNase and less uptake into the cells of the free CpG ODNs, the development of positively charged carriers is necessary for the effective delivery of CpG ODNs into immune cells. Chitosan nanoparticles were prepared by ionic gelation, and the nanoparticles size and surface charge were measured by dynamic light spectroscopy and zeta potential analyzer, respectively. The synthesized chitosan nanoparticles showed two dispersion peaks, at 196 ± 29 nm and 1.33 ± 0.36 μm, with a zeta potential of +3.3 ± 0.4 mV. The toxicity of the chitosan nanoparticles to murine RAW264 macrophages was measured by formazan dye assay utilizing the water-soluble tetrazolium salt WST-8. Our chitosan nanoparticles exhibited no cytotoxicity to RAW264 cells. Finally, we evaluated the immunostimulatory activity of CpG ODNs loaded on chitosan nanoparticles using human peripheral blood mononuclear cells. CpG ODNs significantly enhanced the secretion level of interleukin-6 and interferon-γ by cells compared to the free CpG ODNs. These results indicated that chitosan nanoparticles could be a good candidate for the delivery of CpG ODNs.

Background: Carbonic anhydrases (CAs) are metalloenzymes which catalyze the reversible hydration/dehydration reaction of CO2, in order to maintain the cell homeostasis. These enzymes are found in various tissues and involve in a number of different physiological processes, including ion transport, acid-base balance, bone formation, and gluconeogenesis. Objective: To examine the specific activity of CA and to observe the liver tissue respond to oxidative stress by measured the malondialdehyde (MDA) concentration, in rat liver tissue induced by chronic systemic hypoxia for 1, 3, 5, 7, and 14 days of hypoxia. Results: The study showed that the activity of CA induced by chronic systemic hypoxia significantly increasing at early exposure to the hypoxic condition, at day 1 and days 3 of hypoxia (0.281 and 0.262 nmol/mg protein/minute compared to control 0.155 nmol/mg protein/minute) (p