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The current investigation explores the mechanisms of ammonia and arsenic toxicity, along with high-temperature stress, which other researchers rarely addressed. Pangasianodon hypophthalmus was exposed to low doses of ammonia and arsenic (1/10th of LC50, 2.0 and 2.68 mg L−1, respectively) and high temperature (34 °C) for 105 days. The following treatments were applied: control (unexposed), arsenic (As), ammonia (NH3), ammonia + arsenic (NH3 + As), ammonia + temperature (NH3 + T), and NH3 + As + T. Cortisol levels significantly increased with exposure to ammonia (NH3), arsenic (As), and high temperature (34 °C) compared to the unexposed group. Heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), and metallothionein (MT) gene expressions were notably upregulated by 122–210%, 98–122%, and 64–238%, respectively, compared to the control. Neurotransmitter enzymes (acetylcholine esterase, AChE) were significantly inhibited by NH3 + As + T, followed by other stressor groups. The apoptotic (caspase, Cas 3a and 3b) and detoxifying (cytochrome P450, CYP P450) pathways were substantially affected by the NH3 + As + T group. Immune (total immunoglobulin, Ig; tumor necrosis factor TNFα; and interleukin IL) and growth-related genes (growth hormone, GH; growth hormone regulator, GHR1 and GHRβ; myostatin, MYST and somatostatin, SMT) were noticeably upregulated by NH3 + As + T, followed by other stress groups, compared to the control group. Weight gain %, protein efficiency ratio, feed efficiency ratio, specific growth rate, and other growth attributes were significantly affected by low doses of ammonia, arsenic, and high-temperature stress. Albumin, total protein, globulin, A:G ratio, and myeloperoxidase (MPO) were highly affected by the As + NH3 + T group. Blood profiling, including red blood cells (RBC), white blood count (WBC), and hemoglobin (Hb), were also impacted by stressor groups compared to the control group. Genotoxicity, as DNA damage, was significantly higher in groups exposed to NH3 + As + T (89%), NH3 + T (78%), NH3 (73), NH3 + As (71), and As (68%). The bioaccumulation of arsenic was substantially higher in liver and kidney tissues. The present study contributes to understanding the toxicity mechanisms of ammonia and arsenic, as well as high-temperature stress, through different gene expressions, biochemical attributes, genotoxicity, immunological status, and growth performance of P. hypophthalmus. [ABSTRACT FROM AUTHOR]

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1–8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member’s chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.

Apoptosis is a typical programmed death mode with complex molecular regulation mechanisms. Developing advanced strategies to monitor apoptosis progression is conducive to disease treatment related with apoptosis. Herein, we developed a regulator-carrying dual-responsive integrated AuNP composite fluorescence probe for in situ real time monitoring apoptosis progression. The nanoprobe is constructed by modifying specially designed double-stranded DNA (dsDNA) and caspase 3-specific cleavable peptides (pep) to the surface of AuNP. After uptake by cells, the nanoprobe recognizes miRNA 21 and triggers fluorescence recovery, enabling silencing and imaging of the upstream signaling molecule miRNA 21. Once miRNA 21 is silenced, the downstream signaling molecule caspase 3 is activated and cleaves the substrate peptides, and fluorescence is restored for in situ imaging of caspase 3. The apoptosis induced by silencing miRNA 21 has been successfully implemented in HeLa and A549 cells. The expression level of miRNA 21 and corresponding changes of caspase 3 have also been effectively monitored. These results suggested this nanoprobe will be a potential tool for apoptosis-related biomedical research and clinical application. [Display omitted] • A regulator-carrying dual-responsive integrated nanoprobe was proposed. • In situ imaging and silence of miRNA 21 could be achieved by this method. • The monitoring of activated caspase 3 could be achieved by this method. • The method could be used to monitor apoptosis progression. [ABSTRACT FROM AUTHOR]

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment., Competing Interests: The authors declare that they have no competing interests., (© 2024 Duan et al.)