Background: Dunaliella salinais a good model organism for studying salt stress. In order to have a global understanding of the expression profiles ofDunaliella salinain response to hypersaline stress, we performed quantitative transcriptomic analysis ofDunaliella salinaunder hypersaline stress (2.5 M NaCl) of different time duration by the second and third generation sequencing method.Results: Functional enrichment of the up-regulated genes was used to analyze the expression profiles. The enrichment of photosynthesis was observed, accompanied by enrichments of carbon fixation, pigment biosynthetic process and heme biosynthetic process, which also imply the enhancement of photosynthesis. Genes responsible for starch hydrolysis and glycerol synthesis were significantly up-regulated. The enrichment of biosynthesis of unsaturated fatty acids implies the plasma membrane undergoes changes in desaturation pattern. The enrichment of endocytosis implies the degradation of plasma membrane and might help the synthesis of new glycerophospholipid with unsaturated fatty acids. Co-enrichments of protein synthesis and degradation imply a higher protein turnover rate. The enrichments of spliceosome and protein processing in endoplasmic reticulum imply the enhancement of regulations at post-transcriptional and post-translational level. No up-regulation of any Na⁺or Cl⁻channels or transporters was detected, which implies that the extra exclusion of the ions by membrane transporters is possibly not needed. Voltage gated Na⁺and Cl⁻channels, mechanosensitive ion channel are possible signal receptors of salt stress, and Ca²⁺and MAP kinase pathways might play a role in signal transduction.Conclusion: At global transcriptomic level, the response ofDunaliella salinato hypersaline stress is a systematic work, possibly involving enhancements of photosynthesis, carbon fixation, and heme biosynthetic process, acceleration of protein turnover, spliceosome, protein processing in endoplasmic reticulum, and endocytosis, as well as degradation of starch, synthesis of glycerol, membrane lipid desaturation. Altogether, the changes of these biological processes occurred at trancriptomic level will help understand how a new intracellular balance achieved inDunaliella salinato adapt to hypersaline environment, which are worth being confirmed at the physiological levels.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease that may lead to joint damage, deformity, and disability, if not treated effectively. Hedyotis diffusa Willd (HDW) and its main components have been widely used to treat a variety of tumors and inflammatory diseases. The present study utilized a network pharmacology approach, microarray data analysis and molecular docking to predict the key active ingredients and mechanisms of HDW against RA. Eleven active ingredients in HDW and 180 potential anti-RA targets were identified. The ingredients-targets-RA network showed that stigmasterol, beta-sitosterol, quercetin, kaempferol, and 2-methoxy-3-methyl-9,10-anthraquinone were key components for RA treatment. KEGG pathway results revealed that the 180 potential targets were inflammatory-related pathways with predominant enrichment of the AGE-RAGE, TNF, IL17, and PI3K-Akt signaling pathways. Screened through the PPI network and with Cytoscape software, RELA, TNF, IL6, TP53, MAPK1, AKT1, IL10, and ESR1 were identified as the hub targets in the HDW for RA treatment. Molecular docking was used to identify the binding of 5 key components and the 8 related-RA hub targets. Moreover, the results of network pharmacology were verified by vitro experiments. HDW inhibits cell proliferation in MH7A cells in a dose and time-dependent manner. RT-qPCR and WB results suggest that HDW may affect hub targets through PI3K/AKT signaling pathway, thereby exerting anti-RA effect. This study provides evidence for a clinical effect of HDW on RA and a research basis for further investigation into the active ingredients and mechanisms of HDW against RA.

Using the halotolerant green microalgae Dunaliella salina as a model organism has special merits, such as a wide range of salt tolerance, unicellular organism, and simple life cycle and growth conditions. These unique characteristics make it suitable for salt stress study. In order to provide an overview of the response of Dunaliella salina to salt stress and hopefully to reveal evolutionarily conserved mechanisms of photosynthetic organisms in response to salt stress, the transcriptomes and the genome of the algae were sequenced by the second and the third-generation sequencing technologies, then the transcriptomes under salt stress were compared to the transcriptomes under non-salt stress with the newly sequenced genome as the reference genome. The major cellular biological processes that being regulated in response to salt stress, include transcription, protein synthesis, protein degradation, protein folding, protein modification, protein transport, cellular component organization, cell redox homeostasis, DNA repair, glycerol synthesis, energy metabolism, lipid metabolism, and ion homeostasis. This study gives a comprehensive overview of how Dunaliella salina responses to salt stress at transcriptomic level, especially characterized by the nearly ubiquitous up-regulation of the genes involving in protein folding, DNA repair, and cell redox homeostasis, which may confer the algae important mechanisms to survive under salt stress. The three fundamental biological processes, which face huge challenges under salt stress, are ignored by most scientists and are worth further deep study to provide useful information for breeding economic important plants competent in tolerating salt stress, other than only depending on the commonly acknowledged osmotic balance and ion homeostasis.

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

The Warburg effect, a hallmark of cancer, positions lactate dehydrogenase (LDH) as a key therapeutic target. Mammals possess three LDH isozymes (LDH-A, LDH-B, LDH-C) with distinct properties. This review critically re-evaluates the simplistic 'aerobic-anaerobic' paradigm, emphasizing that all isozymes catalyze reversible pyruvate-lactate conversion and contribute to tumor metabolism in a context-dependent manner. While LDH-A inhibition is a primary focus, challenges include metabolic plasticity and compensatory LDH-B upregulation. LDH-B plays a critical role in mitochondrial lactate oxidation. We highlight LDH-C as a compelling cancer/testis antigen target. Beyond glycolysis, LDH-C exhibits unique substrate promiscuity, generating oncometabolites like s-2-hydroxyglutarate from α-ketoglutarate. Its structural distinctions and restricted normal tissue expression offer opportunities for highly selective therapy. A comprehensive understanding of all three isozymes is essential for developing effective metabolic interventions against cancer.

Background: Cervical cancer is among the most prevalent malignancies affecting women globally. This study examines the anti-tumor effects and mechanisms of Hedyotis diffusa Willd (HDW), a traditional Chinese medicinal herb, on cervical cancer. Methods: The effects of HDW on the proliferation and migration of SiHa and CaSki cells were evaluated through in vitro assays. Additionally, the anti-tumor activity of HDW was assessed in vivo using a xenograft mouse model. To further explore its potential mechanisms, the effects of HDW on apoptosis, the cell cycle, and the IL-17/NF-κB signaling pathway were analyzed. Results: In vitro, HDW dose-dependently reduced the proliferation, colony formation, and migration of SiHa and CaSki cervical cancer cells (P < 0.01). It induced apoptosis by modulating the expression of BCL2, BAX, caspase 3, and cleaved-caspase 3, and caused S-phase cell cycle arrest through suppression of CDK2 and cyclin A (P < 0.05 or P < 0.01). Hedyotis diffusa Willd also inhibited the IL-17/NF-κB signaling pathway by reducing IL-17A and phosphorylated NF-κB p65 expression (P < 0.05 or P < 0.01). In vivo, HDW significantly inhibited tumor growth in a xenograft mouse model (n = 5), with no signs of systemic toxicity, as demonstrated by stable body weight. Conclusions: These findings suggest that HDW exerts its anti-tumor effects by inducing apoptosis, causing cell cycle arrest, and inhibiting the IL-17/NF-κB signaling pathway, highlighting its potential as a promising therapeutic candidate for cervical cancer.