Srikanth Karnati

Barth Syndrome (BTHS) is an inherited mitochondrial cardiomyopathy caused by variants in the gene encoding TAFAZZIN ( Taz ), a transacylase catalyzing the synthesis of the essential mitochondrial phospholipid cardiolipin (CL). Although defects in Taz deteriorate mitochondrial respiration, Ca ²⁺ -uptake, and redox regulation in cardiac myocytes, we previously observed an unexpected lack of oxidative cardiac damage, despite the development of cardiomyopathy in a BTHS mouse model with Taz -knockdown (KD). Furthermore, we revealed that the integrated stress response (ISR) governs metabolic rewiring in Taz -KD hearts to compensate for deficient mitochondrial FAO and to support GSH production. Here, we interrogated whether adaptive mechanisms in peroxisomes, which are closely associated with mitochondria and harbor antioxidative enzymes, can also compensate for the mitochondrial defects. We identified alterations in the peroxisomal biogenesis factors PEX14 and PEX19, indicating changes in the peroxisomal proteome in Taz -KD vs. WT hearts. While the enzymes of peroxisomal FAO were unchanged, levels of Lon Protease 2 (LONP2) and catalase were elevated in Taz -KD hearts. Inhibition or siRNA-mediated knockdown of catalase increased reactive oxygen species (ROS) and blunted the protection of mouse embryonic fibroblasts (MEF) with Taz -knockout (KO), but not in WT, from ROS-induced activation of the apoptotic caspase 3. Furthermore, we observed that the increase in plasmalogen synthesis in cardiac Taz -KD peroxisomes contributes to the activation of the ISR, since siRNA-mediated knockdown of the key enzyme GNPAT blunted the ISR and thereby increased cellular ROS in Taz -KO, but not WT MEFs. In conclusion, peroxisomes facilitate a counterregulatory response to dysfunctional mitochondria by activating a catalase-driven ROS defense and maintaining ISR-mediated metabolic alterations, both of which compensate for mitochondrial dysfunction and oxidative stress. Therefore, the so far poorly investigated mitochondrial-peroxisome crosstalk may represent a novel therapeutic target in an orphan disease with a poor prognosis.

Macrophages are versatile immune cells capable of modifying their functions based on their location and the specific requirements of the immune response. They polarize into the M1 phenotype when stimulated by inflammatory agents. In contrast to resolve inflammation and to facilitate tissue repair, macrophages polarize into the M2 phenotype. Polarization alters the cellular composition of the macrophages, including peroxisomes and peroxisome proliferator-activated receptors (PPARs). In macrophages, peroxisomes and PPARs perform at least three key roles: mediating inflammation, reducing oxidative stress, and regulating lipid metabolism. We review the functional role of peroxisomes and PPARs on macrophage biology focusing on adaptive mechanisms during these processes. The insights gained from this analysis are expected to lead to new advancements in treating inflammation and immune-related disorders, including autoimmune disorders, metabolic inflammation, and neurodegenerative conditions.

Koi (Cyprinus rubrofuscus Lacepede, 1803) is a highly favored ornamental fish due to its beauty and wide range of variations in Indonesia, categorized by color, patterns, and scales. Some variants are distinguished by color, while others, such as Ginrin, Doitsu, and Shusui, have unique scale types. Despite visible differences, microscopic scale variations remain unexplored. SEM studies in other fish species offer insights into scale ultrastructure, providing opportunities for comparison. Therefore, this study aimed to uncover the microscopic structure of four types of koi fish, namely Doitsu, Ginrin, Shusui, and common scale. Koi fish were obtained from breeders in Yogyakarta, Indonesia, and acclimatized in an aquarium. Scale extraction was conducted under anesthesia using MS-222 and the cleaned scales were then subjected to dehydration, fixation, and affixed to double-sided adhesive tape for SEM analysis. Furthermore, coating with conductive gold enabled observation using SEM at 10 kV, allowing examination of scale features such as focus, radii, circuli, and lepidonts at various magnifications. The results showed that based on SEM analysis, significant differences were observed in scale structures among koi variants. At low magnification, differences in tubercles and lepidonts were observed, particularly between common and Ginrin scale types. Shusui scale showed unique characteristics with a closer arrangement of circuli and distinctive lepidont shapes. At higher magnification, clearer details of radii, circuli, and lepidonts were observed, further highlighting the differences among koi variants. SEM provides crucial insights into the morphology of scales in koi fish variants, showing unseen macroscopic differences and distinct features such as tubercles and lepidont frequency.

The Koi fish (Cyprinus carpio var. koi) is an ornamental fish with a high selling value because of its attractive colors, color patterns, body shape, and swimming motion. Koi fish is extensively traded in the international fish market because of their popularity among hobbyists from numerous countries worldwide. This review discusses various aspects of Koi fish cultivation, including genetic involvement, selective breeding strategies, and management systems. By examining crucial factors such as water parameters, technological innovations, and evolving cultivation methods, this review explored their influence on the quality of Koi fish. Breakthrough technologies, such as ornamental fish warehousing and recirculation aquaculture systems, enhance breeding efficiency and profitability. Molecular sexing, feed optimization, and color enhancement strategies are central to pursuing superior Koi fish. Reproduction management, disease prevention, and risk reduction during transport underscore ongoing efforts to ensure their survival. Despite notable progress, several challenges remain, including limited genetic studies, gaps in disease research, and unexplored herbal alternatives. The active involvement of hobbyists and breeders in research initiatives is a pivotal force in unlocking the untapped potential. The holistic approaches to enhance production efficiency and improve care standards require further exploration, paving the way for a sustainable future in the evolving management of Koi fish cultivation. Keywords: cultivation efficiency, Cyprinus carpio var. koi, sustainable management system.

Barth Syndrome (BTHS) is a rare X-linked disease, characterized clinically by cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the phospholipid acyltransferase tafazzin (Gene: TAFAZZIN, TAZ). Tafazzin catalyzes the final step in the remodeling of cardiolipin (CL), a glycerophospholipid located in the inner mitochondrial membrane. As the phospholipid composition strongly determines membrane properties, correct biosynthesis of CL and other membrane lipids is essential for mitochondrial function. Mitochondria provide 95% of the energy demand in the heart, particularly due to their role in fatty acid oxidation. Alterations in lipid homeostasis in BTHS have an impact on mitochondrial membrane proteins and thereby contribute to cardiomyopathy. We analyzed a transgenic TAFAZZIN-knockdown (TAZ-KD) BTHS mouse model and determined the distribution of 193 individual lipid species in TAZ-KD and WT hearts at 10 and 50 weeks of age, using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Our results revealed significant lipid composition differences between the TAZ-KD and WT groups, indicating genotype-dependent alterations in most analyzed lipid species. Significant changes in the myocardial lipidome were identified in both young animals without cardiomyopathy and older animals with heart failure. Notable alterations were found in phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC) and plasmalogen species. PC species with 2–4 double bonds were significantly increased, while polyunsaturated PC species showed a significant decrease in TAZ-KD mice. Furthermore, Linoleic acid (LA, 18:2) containing PC and PE species, as well as arachidonic acid (AA, 20:4) containing PE 38:4 species are increased in TAZ-KD. We found higher levels of AA containing LPE and PE-based plasmalogens (PE P-). Furthermore, we are the first to show significant changes in sphingomyelin (SM) and ceramide (Cer) lipid species Very long-chained SM species are accumulating in TAZ-KD hearts, whereas long-chained Cer and several hexosyl ceramides (HexCer) species accumulate only in 50-week-old TAZ-KD hearts These findings offer potential avenues for the diagnosis and treatment of BTHS, presenting new possibilities for therapeutic approaches.

BACKGROUND: Lipopolysaccharide (LPS) has been reported to increase CD4+ regulatory T-cell (CD4+ Treg) populations. Acetylsalicylic acid (ASA) has been reported to have immunomodulatory activity, but it may induce chronic gastric ulceration. Another salicylic acid-bearing compound, 2-(3-(chloromethyl)benzoyloxy)benzoic acid (3-CH2Cl), has been reported to have less gastric mucosal damage. However, the effect of 3-CH2Cl on CD4+ Tregs in LPS-induced mice is still unknown. Therefore, the present study was conducted to investigate the immunomodulatory effect of 3-CH2Cl on CD4+ T-cell and CD4+ Treg populations as well as FoxP3 expression in LPS-induced mice.METHODS: Synthesis of 3-CH2Cl was performed by mixing salicylic acid and chloromethylbenzoylchloride with the catalyzation of pyridine, acetone and heat. The 3-CH2Cl tablets were prepared using direct compression method. After intraperitoneal injection of 1 mg/kg BW LPS to mice, 60 mg/kg BW ASA or 60 mg/kg BW 3-CH2Cl was given orally for 3 days. The splenocyte was obtained through splenectomy and collagenase digestion. The population of CD4+ T-cells and CD4+ Tregs, as well as the splenic FoxP3 expression were determined using flow cytometry technique.RESULTS: CD4+ T-cell populations in mice treated with LPS and 3-CH2Cl or ASA were lower than those treated with LPS merely. Meanwhile, CD4+ Treg populations and FoxP3 expression levels in mice treated with LPS and 3-CH2Cl or ASA were higher than those treated with LPS merely.CONCLUSION: Since 3-CH2Cl could decrease CD4+ T-cell population and increase CD4+ Treg population mediated by the increase of FoxP3 expression in LPS-induced inflammation, it may act as a potential therapeutic drug to reduce inflammatory conditions.KEYWORDS: 2-(3-(chloromethyl)benzoyloxy)benzoic acid, acetylsalicylic acid, CD4, T-regulatory cells, FoxP3, LPS

Neurotropic viruses target the central nervous system through various mechanisms: they have the potential to modulate synaptic plasticity, causing cognitive impairments by blocking N-methyl d-aspar... Plain language summary The human brain consists of a complex network of cells called neurons. These neurons communicate with each other through chemicals known as neurotransmitters. Changes in thes... Graphical abstract

The tendency of herpesvirus proteins, such as HCMV-vMIA and KSHV vFLIP, to interact with PEX19 and further interplay with MAVS is crucial. Investigating other herpesviral proteins that tend to interact with PEX19, and MAVS could provide an idea of whether this is a pan-herpesviral strategy.

Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.