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MenSCs Transplantation Improve the Viability of Injured Endometrial Cells Through Activating PI3K/Akt Pathway

Zhang S, Zhang R, Yin X, Lu Y, Cheng H, Pan Y, et al.

Reprod Sci, 2023 Nov;30(11):3325-3338.
PMID: 37308799 DOI: 10.1007/s43032-023-01282-0

Endometrial injury is one of the leading causes of female infertility and is caused by intrauterine surgery, endometrial infection, repeated abortion, or genital tuberculosis. Currently, there is little effective treatment to restore the fertility of patients with severe intrauterine adhesions and thin endometrium. Recent studies have confirmed the promising therapeutic effects of mesenchymal stem cell transplantation on various diseases with definite tissue injury. The aim of this study is to investigate the improvements of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on functional restoration in the endometrium of mouse model. Therefore, ethanol-induced endometrial injury mouse models were randomly divided into two groups: the PBS-treated group, and the MenSCs-treated group. As expected, the endometrial thickness and gland number in the endometrium of MenSCs-treated mice were significantly improved compared to those of PBS-treated mice (P

Matched MeSH terms: Endometrium/metabolism; Phosphatidylinositol 3-Kinases/metabolism
A Case Report of a Rare ER+, PR- Pure Metaplastic Breast Squamous Cell Carcinoma with HER2 Overexpression

Adam SA, Kamaruddin KN, Abd Shukor N, Abdullah Suhaimi SN, Ismail F, Md Yasin M

Am J Case Rep, 2023 Dec 04;24:e941448.
PMID: 38048289 DOI: 10.12659/AJCR.941448

BACKGROUND Breast squamous cell carcinoma (SCC) is a subtype of metaplastic breast carcinoma (MBC), which is a rare malignancy and accounts for 0.1% of all invasive breast carcinomas. Guidelines on definitive management and treatment of breast SCC are not well established, given its rarity and diverse immunohistochemistry (IHC) profile, and lack of clinical data. Most cases of breast SCC are triple-negative breast cancer - negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This case report outlines the clinicopathological profile of a pure breast SCC case with a rare IHC profile; HER2 and ER positive. CASE REPORT A 41-year-old woman presented with a right breast mass that had been growing for 2 months. Biopsy confirmed breast SCC, a rare malignancy with IHC profile as follows: HER2 overexpression, ER positive, and PR negative. She underwent neoadjuvant chemotherapy for 3 months followed by right mastectomy with axillary clearance, adjuvant radiotherapy, and oral tamoxifen therapy. Unfortunately, she did not receive anti-HER2 therapy. She developed early locoregional recurrence at 2 months postoperatively, which was treated with excision of the right chest wall and transverse rectus abdominis musculocutaneous (TRAM) flap. She developed liver and lung metastasis and succumbed to her disease at 15 months post-diagnosis. CONCLUSIONS Breast SCC is a rare and aggressive tumor with heterogeneous clinicopathological features. Available guidelines do not outline the definitive treatment for breast SCC, given its rarity and heterogenous IHC profile, leading to a general lack of clinical data. Hence, due to the challenges in managing this rare condition, treatment modalities need to be individualized.

Matched MeSH terms: Receptors, Estrogen/metabolism; Receptors, Progesterone/metabolism
Bacillus cereus: A review of "fried rice syndrome" causative agents

Leong SS, Korel F, King JH

Microb Pathog, 2023 Dec;185:106418.
PMID: 37866551 DOI: 10.1016/j.micpath.2023.106418

"Fried rice syndrome" originated from the first exposure to a fried rice dish contaminated with Bacillus cereus. This review compiles available data on the prevalence of B. cereus outbreak cases that occurred between 1984 and 2019. The outcome of B. cereus illness varies dramatically depending on the pathogenic strain encounter and the host's immune system. B. cereus causes a self-limiting, diarrheal illness caused by heat-resistant enterotoxin proteins, and an emetic illness caused by the deadly toxin named cereulide. The toxins together with their extrinsic factors are discussed. The possibility of more contamination of B. cereus in protein-rich food has also been shown. Therefore, the aim of this review is to summarize the available data, focusing mainly on B. cereus physiology as the causative agent for "fried rice syndrome." This review emphasizes the prevalence of B. cereus in starchy food contamination and outbreak cases reported, the virulence of both enterotoxins and emetic toxins produced, and the possibility of contaminated in protein-rich food. The impact of emetic or enterotoxin-producing B. cereus on public health cannot be neglected. Thus, it is essential to constantly monitor for B. cereus contamination during food handling and hygiene practices for food product preparation.

Matched MeSH terms: Bacillus cereus/metabolism; Emetics/metabolism
Fulltext Physiological roles for the subfornical organ: a dynamic transcriptome shaped by autonomic state

Hindmarch CC, Ferguson AV

J Physiol, 2016 Mar 15;594(6):1581-9.
PMID: 26227400 DOI: 10.1113/JP270726

The subfornical organ (SFO) is a circumventricular organ recognized for its ability to sense and integrate hydromineral and hormonal circulating fluid balance signals, information which is transmitted to central autonomic nuclei to which SFO neurons project. While the role of SFO was once synonymous with physiological responses to osmotic, volumetric and cardiovascular challenge, recent data suggest that SFO neurons also sense and integrate information from circulating signals of metabolic status. Using microarrays, we have confirmed the expression of receptors already described in the SFO, and identified many novel transcripts expressed in this circumventricular organ including receptors for many of the critical circulating energy balance signals such as adiponectin, apelin, endocannabinoids, leptin, insulin and peptide YY. This transcriptome analysis also identified SFO transcripts, the expressions of which are significantly changed by either 72 h dehydration, or 48 h starvation, compared to fed and euhydrated controls. Expression and potential roles for many of these targets are yet to be confirmed and elucidated. Subsequent validation of data for adiponectin and leptin receptors confirmed that receptors for both are expressed in the SFO, that discrete populations of neurons in this tissue are functionally responsive to these adipokines, and that such responsiveness is regulated by physiological state. Thus, transcriptomic analysis offers great promise for understanding the integrative complexity of these physiological systems, especially with development of technologies allowing description of the entire transcriptome of single, carefully phenotyped, SFO neurons. These data will ultimately elucidate mechanisms through which these uniquely positioned neurons respond to and integrate complex circulating signals.

Matched MeSH terms: Energy Metabolism; Subfornical Organ/metabolism*
Combined toxic effects of nanoplastics and norfloxacin on antioxidant and immune genes in mussels

Ma Y, Gao Y, Xu R, Li D, Waiho K, Wang Y, et al.

Mar Environ Res, 2024 Jan;193:106277.
PMID: 38040551 DOI: 10.1016/j.marenvres.2023.106277

Nanoplastics (NPs) and antibiotics (ABs) are two of the emerging marine contaminants that have drawn the most attention in recent years. Given the necessity of figuring out the effects of plastic and antibiotic contamination on marine organism life and population in the natural environment, it is essential to apply rapid and effective biological indicators to evaluate their comprehensive toxic effects. In this study, using mussel (Mytilus coruscus) as a model, we investigated the combined toxic effects of NP (80 nm polystyrene beads) and AB (Norfloxacin, NOR) at environmental-relevant concentrations on antioxidant and immune genes. In terms of the antioxidant genes, NPs significantly increased the relative expression of Cytochrome P450 3A-1 (CYP3A-1) under various concentrations of NOR conditions, but they only significantly increased the relative expression of CYP3A-2 in the high concentration (500 μg L-1 NOR) co-exposure group. In the NP-exposure group which exposed to no or low concentrations of NOR, nuclear factor erythroid 2-related factor 2 (Nrf2) was upregulated. In terms of the immune genes, interleukin-1 receptor-associated kinase (IRAK) -1 showed a significant increase in the low-concentration NOR group while a significant inhibition in the high-concentration NOR group. Due to the presence of NPs, exposure to NOR resulted in a significant increase in both IRAK-4 and heat shock protein (HSP) 70. Our findings indicate that polystyrene NPs can exacerbate the effects of NOR on the anti-oxidant and immune defense performance of mussels. This study delves into the toxic effects of NPs and ABs from a molecular perspective. Given the expected increase in environmental pollution due to NPs and ABs, future research is needed to investigate the potential synergistic effect of NPs and ABs on other organisms.

Matched MeSH terms: Norfloxacin/metabolism; Cytochrome P-450 CYP3A/metabolism
Selection and characterization of ssDNA aptamer targeting Macrobrachium rosenbergii nodavirus capsid protein: A potential capture agent in gold-nanoparticle-based aptasensor for viral protein detection

Ghadin N, Yusof NAM, Syarul Nataqain B, Raston NHA, Low CF

J Fish Dis, 2024 Feb;47(2):e13892.
PMID: 38014615 DOI: 10.1111/jfd.13892

The giant freshwater prawn holds a significant position as a valuable crustacean species cultivated in the aquaculture industry, particularly well-known and demanded among the Southeast Asian countries. Aquaculture production of this species has been impacted by Macrobrachium rosenbergii nodavirus (MrNV) infection, which particularly affects the larvae and post-larvae stages of the prawn. The infection has been recorded to cause mortality rates of up to 100% among the affected prawns. A simple, fast, and easy to deploy on-site detection or diagnostic method is crucial for early detection of MrNV to control the disease outbreak. In the present study, novel single-stranded DNA aptamers targeting the MrNV capsid protein were identified using the systematic evolution of ligands by exponential enrichment (SELEX) approach. The aptamer was then conjugated with the citrate-capped gold nanoparticles (AuNPs), and the sensitivity of this AuNP-based aptasensor for the detection of MrNV capsid protein was evaluated. Findings revealed that the aptamer candidate, APT-MrNV-CP-1 was enriched throughout the SELEX cycle 4, 9, and 12 with the sequence percentage of 1.76%, 9.09%, and 12.42%, respectively. The conjugation of APT-MrNV-CP-1 with citrate-capped AuNPs exhibited the highest sensitivity in detecting the MrNV capsid protein, where the presence of 62.5 nM of the viral capsid protein led to a significant agglomeration of the AuNPs. This study demonstrated the practicality of an AuNP-based aptasensor for disease diagnosis, particularly for detecting MrNV infection in giant freshwater prawns.

Matched MeSH terms: Citrates/metabolism; Capsid Proteins/metabolism
Effects of dietary hydrolysate supplementation on growth, body composition, hematological responses, and liver histology of juvenile giant trevally (Caranx ignobilis Forsskal, 1775)

Nguyen MC, Fotedar R, Pham HD

J Fish Biol, 2024 Jan;104(1):216-226.
PMID: 37800368 DOI: 10.1111/jfb.15580

A feeding study was conducted to investigate how fish protein hydrolysate (FPH) supplementation affected the growth, feed utilization, body composition, and hematology of juvenile giant trevally (Caranx ignobilis Forsskal, 1775). Seven isonitrogenous (52% protein) and isocaloric diets (10% lipid) were formulated, wherein shrimp hydrolysate (SH) and tuna hydrolysate (TH) were used to replace fishmeal at inclusion levels of 0 (control), 30, 60, and 90 g/kg and labeled as control, SH30, SH60, SH90, TH30, TH60, and TH90, respectively. Each diet was fed to triplicate groups of juvenile giant trevally for 8 weeks. The results showed higher final body weight and specific growth rate in fish fed SH30, SH60, TH30, and TH60 than fed control diet. No difference was observed in feed intake, but reduced feed conversion ratio (FCR) was found in fish fed SH30, SH60, TH30, and TH60, demonstrating these diets improved feed utilization. TH90 caused deposition of lipid droplet in the hepatocyte, a sign of liver damage. Total monounsaturated fatty acids, polyunsaturated fatty acids (PUFA), and highly unsaturated fatty acids in fish were not affected by FPH supplementation. Fish fed TH30 showed lower ∑n - 3 PUFA than the fish fed remaining dietary treatments. The elevated serum protein was seen in fish fed control, SH30, SH60, and TH30, demonstrating that these diets were beneficial for the innate immune response in giant trevally. The results indicate that TH and SH could be incorporated into diets of giant trevally at 30-60 g/kg, replacing 7%-13% fishmeal with enhanced growth and health benefits.

Matched MeSH terms: Fatty Acids, Unsaturated/metabolism; Tuna/metabolism
Proteomes of plasmodium knowlesi early and late ring-stage parasites and infected host erythrocytes

Anderson DC, Peterson MS, Lapp SA, Galinski MR

J Proteomics, 2024 Jun 30;302:105197.
PMID: 38759952 DOI: 10.1016/j.jprot.2024.105197

The emerging malaria parasite Plasmodium knowlesi threatens the goal of worldwide malaria elimination due to its zoonotic spread in Southeast Asia. After brief ex-vivo culture we used 2D LC/MS/MS to examine the early and late ring stages of infected Macaca mulatta red blood cells harboring P. knowlesi. The M. mulatta clathrin heavy chain and T-cell and macrophage inhibitor ERMAP were overexpressed in the early ring stage; glutaredoxin 3 was overexpressed in the late ring stage; GO term differential enrichments included response to oxidative stress and the cortical cytoskeleton in the early ring stage. P. knowlesi clathrin heavy chain and 60S acidic ribosomal protein P2 were overexpressed in the late ring stage; GO term differential enrichments included vacuoles in the early ring stage, ribosomes and translation in the late ring stage, and Golgi- and COPI-coated vesicles, proteasomes, nucleosomes, vacuoles, ion-, peptide-, protein-, nucleocytoplasmic- and RNA-transport, antioxidant activity and glycolysis in both stages. SIGNIFICANCE: Due to its zoonotic spread, cases of the emerging human pathogen Plasmodium knowlesi in southeast Asia, and particularly in Malaysia, threaten regional and worldwide goals for malaria elimination. Infection by this parasite can be fatal to humans, and can be associated with significant morbidity. Due to zoonotic transmission from large macaque reservoirs that are untreatable by drugs, and outdoor biting mosquito vectors that negate use of preventive measures such as bed nets, its containment remains a challenge. Its biology remains incompletely understood. Thus we examine the expressed proteome of the early and late ex-vivo cultured ring stages, the first intraerythrocyte developmental stages after infection of host rhesus macaque erythrocytes. We used GO term enrichment strategies and differential protein expression to compare early and late ring stages. The early ring stage is characterized by the enrichment of P. knowlesi vacuoles, and overexpression of the M. mulatta clathrin heavy chain, important for clathrin-coated pits and vesicles, and clathrin-mediated endocytosis. The M. mulatta protein ERMAP was also overexpressed in the early ring stage, suggesting a potential role in early ring stage inhibition of T-cells and macrophages responding to P. knowlesi infection of reticulocytes. This could allow expansion of the host P. knowlesi cellular niche, allowing parasite adaptation to invasion of a wider age range of RBCs than the preferred young RBCs or reticulocytes, resulting in proliferation and increased pathogenesis in infected humans. Other GO terms differentially enriched in the early ring stage include the M. mulatta cortical cytoskeleton and response to oxidative stress. The late ring stage is characterized by overexpression of the P. knowlesi clathrin heavy chain. Combined with late ring stage GO term enrichment of Golgi-associated and coated vesicles, and enrichment of COPI-coated vesicles in both stages, this suggests the importance to P. knowlesi biology of clathrin-mediated endocytosis. P. knowlesi ribosomes and translation were also differentially enriched in the late ring stage. With expression of a variety of heat shock proteins, these results suggest production of folded parasite proteins is increasing by the late ring stage. M. mulatta endocytosis was differentially enriched in the late ring stage, as were clathrin-coated vesicles and endocytic vesicles. This suggests that M. mulatta clathrin-based endocytosis, perhaps in infected reticulocytes rather than mature RBC, may be an important process in the late ring stage. Additional ring stage biology from enriched GO terms includes M. mulatta proteasomes, protein folding and the chaperonin-containing T complex, actin and cortical actin cytoskeletons. P knowlesi biology also includes proteasomes, as well as nucleosomes, antioxidant activity, a variety of transport processes, glycolysis, vacuoles and protein folding. Mature RBCs have lost internal organelles, suggesting infection here may involve immature reticulocytes still retaining organelles. P. knowlesi parasite proteasomes and translational machinery may be ring stage drug targets for known selective inhibitors of these processes in other Plasmodium species. To our knowledge this is the first examination of more than one timepoint within the ring stage. Our results expand knowledge of both host and parasite proteins, pathways and organelles underlying P. knowlesi ring stage biology.

Matched MeSH terms: Malaria/metabolism; Protozoan Proteins/metabolism
Fulltext Bioactive Compounds of Ganoderma boninense Inhibited Methicillin-Resistant Staphylococcus aureus Growth by Affecting Their Cell Membrane Permeability and Integrity

Chan YS, Chong KP

Molecules, 2022 Jan 27;27(3).
PMID: 35164103 DOI: 10.3390/molecules27030838

Some species of Ganoderma, such as G. lucidum, are well-known as traditional Chinese medicine (TCM), and their pharmacological value was scientifically proven in modern days. However, G. boninense is recognized as an oil palm pathogen, and its biological activity is scarcely reported. Hence, this study aimed to investigate the antibacterial properties of G. boninense fruiting bodies, which formed by condensed mycelial, produced numerous and complex profiles of natural compounds. Extract was cleaned up with normal-phase SPE and its metabolites were analyzed using liquid chromatography-mass spectrometry (LCMS). From the disc diffusion and broth microdilution assays, strong susceptibility was observed in methicillin-resistant Staphylococcus aureus (MRSA) in elute fraction with zone inhibition of 41.08 ± 0.04 mm and MIC value of 0.078 mg mL-1. A total of 23 peaks were detected using MS, which were putatively identified based on their mass-to-charge ratio (m/z), and eight compounds, which include aristolochic acid, aminoimidazole ribotide, lysine sulfonamide 11v, carbocyclic puromycin, fenbendazole, acetylcaranine, tigecycline, and tamoxifen, were reported in earlier literature for their antimicrobial activity. Morphological observation via scanning electron microscope (SEM), cell membrane permeability, and integrity assessment suggest G. boninense extract induces irreversible damage to the cell membrane of MRSA, thus causing cellular lysis and death.

Matched MeSH terms: Cell Membrane/metabolism*; Methicillin-Resistant Staphylococcus aureus/metabolism*
Fulltext Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma

Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3595-3603.
PMID: 37266589 DOI: 10.1007/s00210-023-02553-y

Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial-mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.

Matched MeSH terms: beta Catenin/metabolism; Catenins/metabolism
Fulltext Characterization of two bacterial tyrosinases from the halophilic bacterium Hahella sp. CCB MM4 relevant for phenolic compounds oxidation in wetlands

de Almeida Santos G, Englund ANB, Dalleywater EL, Røhr ÅK

FEBS Open Bio, 2024 Dec;14(12):2038-2058.
PMID: 39382070 DOI: 10.1002/2211-5463.13906

Tyrosinases (TYRs) are type-3 copper proteins that are widely distributed in nature. They can hydroxylate and oxidize phenolic molecules and are mostly known for producing melanins that confer protection against photo induced damage. TYRs are also thought to play an important role in the 'latch mechanism', where high concentrations of phenolic compounds inhibit oxidative decomposition of organic biomass and subsequent CO2 release, especially relevant in wetland environments. In the present study, we describe two TYRs, HcTyr1 and HcTyr2, from halophilic bacterium Hahella sp. CCB MM4 previously isolated at Matang mangrove forest in Perak, Malaysia. The structure of HcTyr1 was determined by X-ray crystallography at a resolution of 1.9 Å and represents an uncharacterized group of prokaryotic TYRs as demonstrated by a sequence similarity network analysis. The genes encoding the enzymes were cloned, expressed, purified and thoroughly characterized by biochemical methods. HcTyr1 was able to self-cleave its lid-domain (LID) in a protease independent manner, whereas the LID of HcTyr2 was essential for activity and stability. Both enzymes showed variable activity in the presence of different metals, surfactants and NaCl, and were able to oxidize lignin constituents. The high salinity tolerance of HcTyr1 indicates that the enzyme can be an efficient catalyst in the habitat of the host.

Matched MeSH terms: Bacterial Proteins/metabolism; Monophenol Monooxygenase/metabolism
Fulltext Cytokine factors present in dengue patient sera induces alterations of junctional proteins in human endothelial cells

Appanna R, Wang SM, Ponnampalavanar SA, Lum LC, Sekaran SD

Am J Trop Med Hyg, 2012 Nov;87(5):936-42.
PMID: 22987650 DOI: 10.4269/ajtmh.2012.11-0606

Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant human cytokines were then tested for roles on inducing vascular permeability by treatment of human umbilical vein endothelial cells. Confocal immunofluorescence staining indicated morphologic alteration of human umbilical vein endothelial cells treated with serum samples from patients with dengue hemorrhagic fever compared with serum samples from healthy persons. The findings suggest that cytokines produced during dengue hemorrhagic infections could induce alterations in the vascular endothelium, which may play a fundamental role in the pathophysiology of dengue.

Matched MeSH terms: Endothelium, Vascular/metabolism*; Endothelial Cells/metabolism
CYP14 family in Caenorhabditis elegans: Mitochondrial function, detoxification, and lifespan

Lim SYM, Pan Y, Alshagga M, Lim W, Cin K, Alshehade SA, et al.

J Appl Toxicol, 2024 Nov;44(11):1647-1656.
PMID: 38472099 DOI: 10.1002/jat.4597

CYP-14 members of the Caenorhabditis elegans (C. elegans) Cytochrome P450 (CYP) enzyme family, plays important roles in mitochondrial dysfunction, detoxification, lipid metabolism, defense and lifespan regulation. The review identifies CYP-14 members: cyp-14A1, cyp-14A2, cyp-14A3, cyp-14A4, cyp-14A5 and their homology with human CYP families. Despite limited studies on C. elegans cyp-14 members, the findings unraveled their complex crosstalk between mitochondrial stress, detoxification mechanisms, and lifespan regulation, emphasizing the complexity of these interconnected pathways as well as how their regulation depends on environmental cues changes including pH, nutrients, ROS and chemical stressors. The review underscores the translational relevance to human health, shedding light on potential human homologues and their implications in age-related, metabolic and respiratory diseases. Among other genes, cyp-14A2 and cyp-14A4 predominate the mitochondrial function, heat resistance, lipid metabolism, detoxification and lifespan pathways. In conclusion, these insights pave the way for future research, offering promising avenues for therapeutic interventions targeting CYP-14 activity to address age-related diseases and promote healthy aging.

Matched MeSH terms: Caenorhabditis elegans Proteins/metabolism; Lipid Metabolism
Enhancing fish sludge bioconversion kinetics for nutrient recovery in aquaponics using a modified biological aerated filter with a novel media of polyhedral hollow spheres

Chen A, Zhang H, Zi Y, Gao Y, Lee CT, Li C

J Environ Manage, 2025 Jan;373:123709.
PMID: 39724672 DOI: 10.1016/j.jenvman.2024.123709

Nutrient recovery from aquaculture sludge is vital for promoting hydroponic plant growth and achieving near-zero solid waste discharge in aquaponic systems. Modified biological aerated filters (MBAFs) are promising because of the dual capabilities of aquaculture sludge collection and aerobic mineralization. However, the bioconversion kinetics, which is indirectly related to the packed media, need to be improved. In this study, a novel polyhedral hollow sphere (PHS) medium was used in an MBAF (MBAF-PHS) to overcome the shortcomings of the current medium, facilitating fish sludge retention and enhancing subsequent bioconversion kinetics for nutrient recovery. An average rate of 36.9 g/d for dry weight of fish sludge was achieved during 29 d of filtration and an average reduction rate of 31.30 g/d during 26 d of bioconversion. The total mass of fish sludge was converted by 76.2% via the co-action of the solubilization of organic solids and degradation of dissolved organic matter. MBAF-PHS was competitive for macronutrient recovery compared with the MBAF-sponge previously used. The ratios of the final concentrations of the macronutrients (P, Mg, and S) to the concentrations in Hoagland solution (Cf/CH, %) were 278.1, 162.8, and 200.9%, respectively, whereas the ratios of N, K, and Ca were 65.9, 37.1, and 51.0%, respectively. High bioconversion kinetics of NO3--N and PO43--P were obtained within 7 d with an MNO3-N/MTN of 79.9% and MPO4-P/MDTP of 80.3%. The nutrient bioconversion of fish sludge was associated with the diversity of the microbial community in the MBAF-PHS, especially the population of nitrogen-removing microbial species that developed after 9 d of mineralization.

Matched MeSH terms: Fishes/metabolism; Nitrogen/metabolism
Fulltext The Role of Cyclin d1 in Radiotherapy Resistance of Advance Stage Nasopharyngeal Carcinoma: A Systematic Review

Romdhoni AC, Rajanagara AS, Albab CF, Waskito LA, Wibowo IN, Yunus MRM

Asian Pac J Cancer Prev, 2024 Jul 01;25(7):2211-2218.
PMID: 39068551 DOI: 10.31557/APJCP.2024.25.7.2211

OBJECTIVE: One of the biggest therapy challenges for nasopharyngeal cancer (NPC) is still radioresistance. The radioresistance in NPC is thought to be caused by cyclin D1 overexpression. The purpose of this study was to determine how cyclin D1 contributes to radiation resistance in NPC.
METHODS: Adhering to the PRISMA guidelines, we systematically reviewed studies on cyclin D1-associated radioresistance in NPC from 2012 until 2023. From our search, 15 studies were included.
RESULTS: Cyclin D1's role in radiotherapy resistance is elucidated through several mechanisms, notably SHP-1 and B-catenin. Overexpression of SHP-1 led to an increase in cyclin D1, a higher proportion of cells in the S-phase, and radioresistance. Conversely, inhibiting β-catenin and cyclin D1 expression enhances radiation sensitivity.
CONCLUSION: In conclusion, Cyclin D1 has a strong correlation with radiation resistance; downregulation of the protein increases radiosensitivity, while overexpression of the protein promotes radioresistance.

Matched MeSH terms: beta Catenin/metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism
Ceramides and Skin Health: New Insights

Yong TL, Zaman R, Rehman N, Tan CK

Exp Dermatol, 2025 Feb;34(2):e70042.
PMID: 39912256 DOI: 10.1111/exd.70042

Ceramide has transitioned from an incidental discovery to a vital element in skincare, becoming a thoroughly studied compound in the quest to treat skin conditions. Creating a moisture barrier, preserving hydration, regulating pH, controlling inflammation, and enhancing skin functions and appearance are among its established benefits. It is often used medically to repair skin barrier defects, as observed in inflammatory skin conditions like atopic dermatitis (AD) and dry skin types. Furthermore, ceramide and its metabolites are commonly used as predictors before disease manifestation and for prognostication processes, thus can be used as biomarker for clinical diagnosis as well. In the last couple of decades, momentum was also seen in the pre-clinical studies involving anti-cancer and nanotechnology field, whereby ceramide was also used as a drug, a carrier, or even adjunct formulation to increase efficacy of treatment such as chemotherapy. Approaches to increase ceramide levels include directly replenishing lost ceramides with natural extracts, synthetic pseudo-ceramides, or ceramide-like analogues, as well as using supplements that stimulate the body's natural ceramide production. Although ceramide is a well-known treatment in skincare and for common skin conditions like AD and psoriasis, its development and related pharmacology for severe skin conditions, such as skin cancer, remain in pre-clinical stages. Hence, the purpose of this research is to explore the role of ceramide in skin health and its application in common skin diseases.

Matched MeSH terms: Psoriasis/metabolism; Skin Neoplasms/metabolism
Fulltext Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Skin Matrix Synthesis and Pigmentation

Kee LT, Foo JB, How CW, Nur Azurah AG, Chan HH, Mohd Yunus MH, et al.

Int J Nanomedicine, 2025;20:1561-1578.
PMID: 39931529 DOI: 10.2147/IJN.S497940

INTRODUCTION: Research has unveiled the remarkable properties of extracellular vesicles derived from mesenchymal stromal cells (MSCs), particularly in promoting wound healing, aiding re-epithelialization, revitalizing aging skin, and inhibiting hyperpigmentation. However, investigations into the potential of small extracellular vesicles from umbilical cord-derived MSCs (UC-MSC-sEVs) in reducing scarring and preventing hyperpigmentation remain limited. Therefore, this study aims to evaluate the impact of UC-MSC-sEVs on the synthesis of the skin's extracellular matrix (ECM) and pigmentation using in vitro models.
METHODS: The study investigated the impact of characterized UC-MSC-sEVs on various aspects including the proliferation, migration, antioxidant activity, and ECM gene expression of human dermal fibroblasts (HDF). Additionally, the effects of UC-MSC-sEVs on the proliferation, melanin content, and tyrosinase (TYR) activity of human melanoma cells (MNT-1) were examined. Furthermore, ex vivo models were employed to evaluate the skin permeation of PKH26-labelled UC-MSC-sEVs.
RESULTS: The findings indicated that a high concentration of UC-MSC-sEVs positively influenced the proliferation of HDF. However, no changes in cell migration rate were observed. While the expressions of collagen type 1 and type 3 remained unaffected by UC-MSC-sEVs treatment, there were dose-dependent increases in the gene expressions of fibronectin, matrix metallopeptidase (MMP) 1, and MMP 3. Furthermore, UC-MSC-sEVs treatment did not impact the antioxidative superoxide dismutase (SOD) expression in HDF. Although UC-MSC-sEVs did not alter the proliferation of MNT-1 cells, it did result in a dose-dependent reduction in melanin synthesis without affecting TYR activity. However, when it was applied topically, UC-MSC-sEVs failed to penetrate the skin barrier and remained localized within the stratum corneum layer even after 18 hours.
CONCLUSION: These results highlight the potential of UC-MSC-sEVs in stimulating HDF proliferation, regulating ECM synthesis, and reducing melanin production. This demonstrates the promising application of UC-MSC-sEVs in medical aesthetics for benefits such as scar reduction, skin rejuvenation, and skin lightening.

Matched MeSH terms: Fibroblasts/metabolism; Monophenol Monooxygenase/metabolism
Proteomic insights into fruit-pathogen interactions: managing biotic stress in fruit

Putra AI, Khan MN, Kamaruddin N, Khairuddin RFR, Al-Obaidi JR, Flores BJ, et al.

Plant Cell Rep, 2025 Feb 13;44(3):54.
PMID: 39945834 DOI: 10.1007/s00299-025-03443-8

Proteomics has revealed complex immune responses in fruits, leading to the identification of potential disease biomarkers and resistance mechanisms. Fruit diseases caused by fungal and bacterial pathogens present critical challenges to global food security by reducing fruit shelf life and quality. This review explores the molecular dynamics of fruit-pathogen interactions using advanced proteomic techniques. These approaches include mass spectrometry-based identification, gel-based, and gel-free strategies, tailored to the unique compositions of fruit tissues for accurate protein extraction and identification. Proteomic studies reveal pathogen-induced changes in fruit proteomes, including the upregulation of defence-related proteins and suppression of metabolic pathways crucial for pathogen survival. Case studies on tomatoes, apples, and bananas highlight specific pathogen-responsive proteins, such as PR proteins and enzymes involved in ROS scavenging, which play roles in disease resistance mechanisms. The review further demonstrates the utility of proteomic data in identifying early disease biomarkers, guiding genetic improvements for disease resistance, and optimizing pathogen control measures. Integrating proteomic insights with transcriptomics and metabolomics provides a multidimensional understanding of fruit-pathogen interactions, paving the way for innovative solutions in agriculture. Future research should prioritize multi-omics approaches and field-level validations to translate laboratory findings into practical applications. The advancements discussed underscore the transformative role of proteomics in improving food security and sustainability amid challenges posed by climate change and increasing global food demand.

Matched MeSH terms: Plant Proteins/metabolism; Malus/metabolism
Fulltext Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model

Garza-Manero S, Sindi AAA, Mohan G, Rehbini O, Jeantet VHM, Bailo M, et al.

Epigenetics Chromatin, 2019 12 12;12(1):73.
PMID: 31831052 DOI: 10.1186/s13072-019-0320-7

BACKGROUND: Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells.
RESULTS: We show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2.
CONCLUSIONS: We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.

Matched MeSH terms: Chromatin/metabolism*; Histones/metabolism; Nerve Tissue Proteins/metabolism; Neurons/metabolism; HMGN1 Protein/metabolism; HMGN2 Protein/metabolism*; Pluripotent Stem Cells/metabolism; Octamer Transcription Factor-3/metabolism; Basic Helix-Loop-Helix Transcription Factors/metabolism; Neural Stem Cells/metabolism; Nanog Homeobox Protein/metabolism
Fulltext Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment

Kumar S, Karuppanan K, Subramaniam G

J Med Virol, 2022 Oct;94(10):4780-4791.
PMID: 35680610 DOI: 10.1002/jmv.27927

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain (RBD) and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild-type (WT). Negative electrostatic potential of N-terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.

Matched MeSH terms: Peptidyl-Dipeptidase A/metabolism; Receptors, Virus/metabolism

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