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We have previously identified Ertredin (3-(2-amino-5-bromophenyl) quinoxalin-2(1H)-one) as a compound that suppresses 3D spheroid formation and tumorigenesis in NIH3T3 cells induced by Epidermal Growth Factor Receptor variant III (EGFRvIII) transduction. One of its targets has been shown to be NDUFA12 (NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex Subunit 12), a component protein of oxidative phosphorylation complex I. In this report, we compared the growth inhibitory activity of Ertredin with its methylated analogue 7MeERT (3-(2-amino-5-bromophenyl)-7-methylquinoxalin-2(1H)-one) on human cancer cells. 7MeERT induced the inhibition of the proliferation of various cancer cells similarly to Ertredin and showed higher activity in glioblastoma cells, A431 cells overexpressing EGFR (wild type), and multiple myeloma cells. Molecular docking analysis and a Cellular Thermal Shift Assay (CETSA) suggested that 7MeERT binds to NDUFA12 similarly to Ertredin. The binding of 7MeERT and Ertredin to NDUFA12 in glioblastoma was further supported by the inhibition of the oxygen consumption rate. These results suggest that 7MeERT also binds to NDUFA12, inhibits oxidative phosphorylation, and has a higher anti-cancer cell growth inhibitory activity than Ertredin. [ABSTRACT FROM AUTHOR]

Zinc (Zn) is a vital trace element that plays a pivotal role in protein synthesis, cellular growth, and differentiation and is involved as a cofactor of metalloenzymes, performing a wide variety of metabolic, immune, and synthesis roles. Zn is required at all stages of an infant's and child's development, and severe Zn deficiency has been reported to lead to slower physical, cognitive, and sexual growth. Preterm neonates are at a higher risk of developing zinc deficiency for a variety of reasons, including low Zn intake from enteral feeds containing breast milk, relative malabsorption due to immaturity of the gastrointestinal tract with limited absorptive capacity, increased urinary loss of zinc, and increased demand during the early developmental stages. Moreover, premature infants are at risk of gastrointestinal diseases like necrotizing enterocolitis (NEC), which can limit absorption capacity and potentially lead to malabsorption. TPN is frequently used in preterm infants to provide them with sufficient nutrients and calories. However, it has its own complications, including cholestasis, especially if used for prolonged periods. In this case report, we are presenting the case of a male preterm infant who was delivered by caesarean section at 26 weeks' gestation. The baby developed an intestinal perforation due to NEC, for which he underwent surgery for resection of the necrotic bowel and the creation of a high ileal stoma and was put on prolonged total parenteral nutrition (TPN), which led to the development of zinc deficiency. [ABSTRACT FROM AUTHOR]

Background: The malignancy of melanoma is attributed to its pronounced invasiveness, extensive vascularization, and rapid tumor cell growth and metastasis. LncRNA SLNCR1 is closely associated with a variety of aggressive tumors. However, our understanding of SLNCR1 influences on malignant melanoma growth metastasis mechanism especially proangiogenic mechanism remains unclear. Methods: The expression of SLNCR1 was evaluated in melanoma tissues, adjacent tissues, melanoma cell lines. The abilities of SLNCR1 on proliferation, migration, and angiogenesis of HUVECs were detected by CCK‐8, flow cytometry, and Western blot assays. The association between SLNCR1, DNMT1, and SPRY2 was assessed by ChIP, RIP, and Western blot assays. The effect of SLNCR1 on tumor growth was determined using a xenograft model in nude mice. Results: SLNCR1 was confirmed to be highly expressed in melanoma tissues and cells. CM from melanoma cells transfected with sh‐SLNCR1 attenuated proliferation, migration, and angiogenesis of HUVECs. Moreover, loss of SLNCR1 hindered tumor growth and metastasis, as evidenced by reduced tumor size and weight, as well as angiogenesis. Mechanistic studies revealed that SLNCR1 silenced SPRY2 expression, likely through enhancing DNMT1‐mediated DNA methylation of SPRY2 promoter. Conclusion: SLNCR1 is an oncogene that interacts with DNMT1 to mediate SPRY2 methylation, thereby suppressing SPRY2 expression and promoting the angiogenesis and tumor growth in melanoma. SLNCR1 may serve as a potential target for melanoma treatment. [ABSTRACT FROM AUTHOR]

Roberts et al. have provided an insightful counterpoint to our review article on the utility of the synergist ablation model. The purpose of this review is to provide some further dialogue regarding the strengths and weaknesses of the synergist ablation model. Specifically, we highlight that the robustness of the model overshadows surgical limitations. We also compare the transcriptomic responses to synergist ablation in mice and resistance exercise in humans to identify common pathways. We conclude that "cell growth is cell growth" and that the mechanisms available to cells to accumulate biomass and increase in size are similar across cell types and independent of the rate of growth. [ABSTRACT FROM AUTHOR]

In industrial fermentation processes, microorganisms often encounter acid stress, which significantly impact their productivity. This study focused on the acid-resistant module composed of small RNA (sRNA) DsrA and the sRNA chaperone Hfq. Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH, but failed to obtain this desired phenotype in industrial strains. Here, we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode. We then assessed the potential of the CymR-based negative auto-regulation (NAR) circuit for industrial application, under different media, strains and pH levels. Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acidresistant circuit to improve the cell growth of E. coli MG1655. This circuit was robust and worked well in the industrial lysine-producing strain E. coli SCEcL3 at a starting pH of 6.8 and without pH control, resulting in a 250 % increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain. This study showed the practical application of NAR circuit in regulating DsrA-Hfq module, effectively and robustly improving the acid tolerance of industrial strains, which provides a new approach for breeding industrial strains with tolerance phenotype. [ABSTRACT FROM AUTHOR]

Avian Pasteurella multocida infection, can cause serious economic losses to the poultry industry every year. The inactivated vaccines of avian Pasteurella multocida are used to prevent infection. Increasing the cell density of avian Pasteurella multocida is the key to the application of these inactivated vaccines. This can be achieved by controlling the feeding strategy. This study aimed to achieve high-cell-density cultivation of avian Pasteurella multocida by applying an appropriate medium and a rational feeding strategy based on viable cell growth and dissolved oxygen level variation during a fermentation process. An optimized medium suited for the growth of avian P. multocida was used. Meanwhile, besides the online real-time determination of viable cell density, the concentration of glucose was maintained at 1.5 g/L using a glucose-stat feeding strategy after 2 h. The selected nutrient mixture, including yeast extract, tryptone, betaine, VB1, and VH, was fed using a dissolved oxygen feedback feeding strategy after 4 h. As a result, the viable cell density and cell count of avian P. multocida under optimized conditions were increased to OD600: 9.38 and 4.58×1010 CFU/mL, which were higher by 7.27 and 7.26 times than those under the original conditions, respectively. [ABSTRACT FROM AUTHOR]

Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration, and invasion of gastric cancer (GC) cells, but the molecular mechanism has not been fully elucidated. This study revealed the oncogenic effects of UCA1 on cell growth and invasion. Furthermore, UCA1 expression was significantly correlated with the overall survival of GC patients, and the clinicopathological indicators, including tumor size, depth of invasion, lymph node metastasis, and TNM stage. Additionally, miR-1-3p was identified as a downstream target of UCA1, which was negatively regulated by UCA1. MiR-1-3p inhibited cell proliferation and vasculogenic mimicry (VM), and induced cell apoptosis by upregulating BAX, BAD, and tumor suppressor TP53 expression levels. Moreover, miR-1-3p almost completely reversed the oncogenic effect caused by UCA1, including cell growth, migration, and VM formation. This study also confirmed that UCA1 promoted tumor growth in vivo. In this study, we also revealed the correlation between UCA1 and VM formation, which is potentially crucial for tumor metastasis. Meanwhile, its downstream target miR-1-3p inhibited VM formation in GC cells. In summary, these findings indicate that the UCA1/miR-1-3p axis is a potential target for GC treatment. [ABSTRACT FROM AUTHOR]

Radiation therapy continues to be the cornerstone treatment for malignant brain tumors, the majority of which express wild-type p53. Therefore, the identification of drugs that promote the ionizing radiation (IR)-induced activation of p53 is expected to increase the efficacy of radiation therapy for these tumors. The growth inhibitory effects of CEP-1347, a known inhibitor of MDM4 expression, on malignant brain tumor cell lines expressing wild-type p53 were examined, alone or in combination with IR, by dye exclusion and/or colony formation assays. The effects of CEP-1347 on the p53 pathway, alone or in combination with IR, were examined by RT-PCR and Western blot analyses. The combination of CEP-1347 and IR activated p53 in malignant brain tumor cells and inhibited their growth more effectively than either alone. Mechanistically, CEP-1347 and IR each reduced MDM4 expression, while their combination did not result in further decreases. CEP-1347 promoted IR-induced Chk2 phosphorylation and increased p53 expression in concert with IR in a Chk2-dependent manner. The present results show, for the first time, that CEP-1347 is capable of promoting Chk2-mediated p53 activation by IR in addition to inhibiting the expression of MDM4 and, thus, CEP-1347 has potential as a radiosensitizer for malignant brain tumors expressing wild-type p53. [ABSTRACT FROM AUTHOR]

Our study highlights the apoptosis, cell cycle, DNA ploidy, and autophagy molecular mechanisms network to identify prostate pathogenesis and its prognostic role. Caspase 3/7 expressions, cell cycle, adhesion glycoproteins, autophagy, nuclear shrinkage, and oxidative stress by flow-cytometry analysis are used to study the BPH microenvironment's heterogeneity. A high late apoptosis expression by caspases 3/7 activity represents an unfavorable prognostic biomarker, a dependent predictor factor for cell adhesion, growth inhibition by arrest in the G2/M phase, and oxidative stress processes network. The heterogeneous aggressive phenotype prostate adenoma primary cell cultures present a high S-phase category (>12%), with an increased risk of death or recurrence due to aneuploid status presence, representing an unfavorable prognostic biomarker, a dependent predictor factor for caspase 3/7 activity (late apoptosis and necrosis), and cell growth inhibition (G2/M arrest)-linked mechanisms. Increased integrin levels in heterogenous BPH cultures suggest epithelial–mesenchymal transition (EMT) that maintains an aggressive phenotype by escaping cell apoptosis, leading to the cell proliferation necessary in prostate cancer (PCa) development. As predictor biomarkers, the biological mechanisms network involved in apoptosis, the cell cycle, and autophagy help to establish patient prognostic survival or target cancer therapy development. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are produced during cellular metabolism and in response to environmental stress. While low levels of ROS play essential physiological roles, excess ROS can damage cellular components, leading to cell death or transformation. ROS can also regulate protein interactions in cancer cells, thereby affecting processes such as cell growth, migration, and angiogenesis. Dysregulated interactions occur via various mechanisms, including amino acid modifications, conformational changes, and alterations in complex stability. Understanding ROS-mediated changes in protein interactions is crucial for targeted cancer therapies. In this review, we examine the role that ROS mechanisms in regulating pathways through protein–protein interactions. [ABSTRACT FROM AUTHOR]

Cancer remains a formidable challenge in the field of medicine, necessitating innovative therapeutic strategies to combat its relentless progression. The cell cycle, a tightly regulated process governing cell growth and division, plays a pivotal role in cancer development. Dysregulation of the cell cycle allows cancer cells to proliferate uncontrollably. Therapeutic interventions designed to disrupt the cell cycle offer promise in restraining tumor growth and progression. Telomerase, an enzyme responsible for maintaining telomere length, is often overactive in cancer cells, conferring them with immortality. Targeting telomerase presents an opportunity to limit the replicative potential of cancer cells and hinder tumor growth. Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis. Strategies aimed at inhibiting angiogenesis seek to deprive tumors of their vital blood supply, thereby impeding their progression. Metastasis, the spread of cancer cells from the primary tumor to distant sites, is a major challenge in cancer therapy. Research efforts are focused on understanding the underlying mechanisms of metastasis and developing interventions to disrupt this deadly process. This review provides a glimpse into the multifaceted approach to cancer therapy, addressing critical aspects of cancer biology—cell cycle regulation, telomerase activity, angiogenesis, and metastasis. Through ongoing research and innovative strategies, the field of oncology continues to advance, offering new hope for improved treatment outcomes and enhanced quality of life for cancer patients. [ABSTRACT FROM AUTHOR]

Deep-sea organisms are subjected to extreme conditions; therefore, understanding their adaptive strategies is crucial. We utilize Saccharomyces cerevisiae as a model to investigate pressure-dependent protein regulation and piezo-adaptation. Using yeast deletion library analysis, we identified 6 poorly characterized genes that are crucial for high-pressure growth, forming novel functional modules associated with cell growth. In this study, we aimed to unravel the molecular mechanisms of high-pressure adaptation in S. cerevisiae , focusing on the role of MTC6. MTC6 , the gene encoding the novel glycoprotein Mtc6/Ehg2, was found to stabilize tryptophan permease Tat2, ensuring efficient tryptophan uptake and growth under high pressure at 25 MPa. The loss of MTC6 led to promoted vacuolar degradation of Tat2, depending on the Rsp5-Bul1 ubiquitin ligase complex. These findings enhance our understanding of deep-sea adaptations and stress biology, with broad implications for biotechnology, environmental microbiology, and evolutionary insights across species. [ABSTRACT FROM AUTHOR]

Background β-lactam antibiotics, which inhibit penicillin-binding protein 3 (PBP3) that is required for cell division, play a key role in treating P. aeruginosa infections. Some sequence variations in PBP3 have been associated with β-lactam resistance but the effects of variations on antibiotic susceptibility and on cell division have not been quantified. Antibiotic efflux can also reduce susceptibility. Objectives To quantify the effects of PBP3 variations on β-lactam susceptibility and cell morphology in P. aeruginosa. Methods Nineteen PBP3 variants were expressed from a plasmid in the reference strain P. aeruginosa PAO1 and genome engineering was used to construct five mutants expressing PBP3 variants from the chromosome. The effects of the variations on β-lactam minimum inhibitory concentration (MIC) and cell morphology were measured. Results Some PBP3 variations reduced susceptibility to a variety of β-lactam antibiotics including meropenem, ceftazidime, cefepime and ticarcillin with different variations affecting different antibiotics. None of the tested variations reduced susceptibility to imipenem or piperacillin. Antibiotic susceptibility was further reduced when PBP3 variants were expressed in mutant bacteria overexpressing the MexAB-OprM efflux pump, with some variations conferring clinical levels of resistance. Some PBP3 variations, and sub-MIC levels of β-lactams, reduced bacterial growth rates and inhibited cell division, causing elongated cells. Conclusions PBP3 variations in P. aeruginosa can increase the MIC of multiple β-lactam antibiotics, although not imipenem or piperacillin. PBP3 variations, or the presence of sub-lethal levels of β-lactams, result in elongated cells indicating that variations reduce the activity of PBP3 and may reduce bacterial fitness. [ABSTRACT FROM AUTHOR]

Background: Tissue stimulations greatly affect cell growth, phenotype, and function, and they play an important role in modeling tissue physiology. With the goal of understanding the cellular mechanisms underlying the response of tissues to external stimulations, in vitro models of tissue stimulation have been developed in hopes of recapitulating in vivo tissue function. Methods: Herein we review the efforts to create and validate tissue stimulators responsive to electrical or mechanical stimulation including tensile, compression, torsion, and shear. Results: Engineered tissue platforms have been designed to allow tissues to be subjected to selected types of mechanical stimulation from simple uniaxial to humanoid robotic stain through equal‐biaxial strain. Similarly, electrical stimulators have been developed to apply selected electrical signal shapes, amplitudes, and load cycles to tissues, lending to usage in stem cell‐derived tissue development, tissue maturation, and tissue functional regeneration. Some stimulators also allow for the observation of tissue morphology in real‐time while cells undergo stimulation. Discussion on the challenges and limitations of tissue simulator development is provided. Conclusions: Despite advances in the development of useful tissue stimulators, opportunities for improvement remain to better reproduce physiological functions by accounting for complex loading cycles, electrical and mechanical induction coupled with biological stimuli, and changes in strain affected by applied inputs. [ABSTRACT FROM AUTHOR]

Novel azo dye ligand [4‐([2,3‐dimethyl‐5‐oxo‐1‐phenyl‐2,5‐dihydro‐1H‐pyrazol‐4‐yl]diazenyl)‐3‐hydroxybenzaldehyde (HL)] and its Co(II), Ni(II), Ru(III), and Zr(IV) metal chelates, were produced and thoroughly described applying modern spectral and analytical approaches. The results showed that HL chelated in tridentate mode, leading to octahedral geometry toward the present metal ions where Co(II), Ni(II), and Zr(IV) complexes exhibit outer sphere hybridization, while the Ru(III) complex exhibits inner sphere hybridization. The calculated particle size values of the complexes reached 41.34, 46.41, 48.67, and 33.37 nm for Co(II), Ni(II), Ru(III), and Zr(IV) chelates, respectively applying the Debye–Scherrer equation on XRD patterns. When compared to its metal complexes, the ligand's antibacterial action against several bacteria demonstrates increased activity. Tests were conducted on A‐549 and PANC‐1 cells to evaluate the compounds' anticancer efficacy against the vinblastine standard. Co(II) nanosized complex exhibited cytotoxicity that was greater than that of the reference medication vinblastine sulfate against A‐549 cell line. It is promising to use the Co(II) complex to create novel anticancer medications. Quantum chemical calculations for ligand and its solid metal complexes were carried out utilizing the DFT of the DMOL3 module. Furthermore, the molecular docking studies were conducted on the A‐549 protein, associated with FGFR1, using the Schrödinger suite. The ligand and the Ru(III) complex exhibit the most potent inhibitory effects on the FGFR1 protein, a receptor tyrosine kinase integral to cellular growth and differentiation. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) signaling has multiple physiological roles in cellular growth, metabolism, and aging. Myocardial hypertrophy, cell death, senescence, fibrosis, and electrical remodeling are hallmarks of various heart diseases and contribute to the progression of heart failure. This review highlights the critical role of IGF-1 and its cognate receptor in cardiac hypertrophy, aging, and remodeling. [ABSTRACT FROM AUTHOR]

Alterations in cell wall composition imply in new structural and functional traits in gall developmental sites, even when the inducer is a sucking exophytophagous insect with strict feeding sites as the aphid associated to Malus domestica Borkh. This host plant is an economically important, fruit-bearing species, susceptible to gall induction by the sucking aphid Eriosoma lanigerum Hausmann, 1802. Herein, the immunocytochemical detection of arabinogalactan-proteins (AGPs), pectins, and hemicelluloses using monoclonal antibodies was performed in samples of non-galled roots and stems, and of root and stem galls on M. domestica. The dynamics of these cell wall components was discussed under the structural and functional traits of the galls proximal, median, and distal regions, according to the proximity of E. lanigerum colony feeding site. In the proximal region, the epitopes of AGPs and homogalacturonans (HGs) are related to cell growth and divisions, which result in the overproduction of parenchyma cells both in root and stem galls. In the proximal and median regions, the co-occurrence of HGs and arabinans in the cell walls of parenchyma and secondary tissues favors the nutrient flow and water-holding capacity, while the xylogalacturonans and hemicelluloses may function as additional carbohydrate resources to E. lanigerum. The immunocytochemical profile of the cell walls support the feeding activity of E. lanigerum mainly in the gall proximal region. The similarity of the cell wall components of the gall distal region and the non-galled portions, both in roots and stems, relates to the decrease of the cecidogenetic field the more distant the E. lanigerum colony is. [ABSTRACT FROM AUTHOR]

Canine urothelial carcinoma (cUC) is one of the most malignant tumors affecting dogs; however, its proliferative mechanism is yet to be fully elucidated. The ubiquitin-proteasome system (UPS) is an important metabolic pathway regulating protein degradation, and its dysfunction leads to apoptosis. We investigated the antitumor effect of the proteasome inhibitor bortezomib, which blocks the UPS. Bortezomib inhibited cell growth in cUC cell lines by inducing apoptosis in vitro. These findings suggest the potential of bortezomib as a novel therapeutic drug for dogs with cUC. [ABSTRACT FROM AUTHOR]

The constitutive and strong GAP promoter (PGAP) from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene has emerged as a suitable option for protein production in methanol-free Komagataella phaffii (syn. Pichia pastoris) expression systems. Nevertheless, the effect of the transcriptional terminator from the alcohol oxidase 1 gene (TAOX1) or GAPDH gene (TGAP) within the heterologous gene structure on the transcriptional activity in a PGAP-based strain and the impact on the extracellular product/biomass yield (Yp/x) has not yet been fully characterized. In this study, we engineered two K. phaffii strains, each harboring a single copy of a different combination of regulatory DNA elements (i.e., PGAP-TAOX1 or PGAP-TGAP pairs) within the heterologous gene structure. Moreover, we assessed the impact of the regulatory element combinations, along with the carbon source (glucose or glycerol) and the stage of cell growth, on the transcript levels of the reporter gene and the endogenous GAPDH gene in the yeast cells, as well as the extracellular Yp/x values. The results indicate that the regulation of transcription for both heterologous and endogenous GAPDH genes, the extracellular Yp/x values, and translation and/or heterologous protein secretion were influenced by the PGAP-transcriptional terminator combination, with the carbon source and the stage of cell growth acting as modulatory factors. The highest transcript levels for the heterologous and endogenous GAPDH genes were observed in glucose cultures at a high specific growth rate (0.253 h−1). Extracellular Yp/x values showed an increasing trend as the culture progressed, with the highest values observed in glucose cultures, and in the PGAP-TAOX1-based strain. The presence of TAOX1 or TGAP within the heterologous gene structure activated distinct gene regulatory elements in each strain, leading to differential modulation of gene regulation for the heterologous and the GAPDH genes, even though both genes were under the control of the same promoter (PGAP). TAOX1 induced competitive regulation of transcriptional activity between the two genes, resulting in enhanced transcriptional activity of the GAPDH gene. Moreover, TAOX1 led to increased mRNA stability and triggered distinct metabolic downregulation mechanisms due to carbon source depletion compared to TGAP. TAOX1 enhanced translation and/or heterologous protein secretion activity at a high specific growth rate (0.253 h−1), while TGAP was more effective in enhancing post-transcriptional activity at a low specific growth rate (0.030 h−1), regardless of the carbon source. The highest extracellular Yp/x was obtained with the PGAP-TAOX1-based strain when the culture was carried out at a low specific growth rate (0.030 h−1) using glucose as the carbon source. The optimization of regulatory elements and growth conditions presents opportunities for enhancing the production of biomolecules of interest. [ABSTRACT FROM AUTHOR]

Media preparation parameters contribute significantly to media quality, cell culture performance, productivity, and product quality. Establishing proper media preparation procedures is critical for ensuring a robust CHO cell culture process. Process analytical technology (PAT) enables unique ways to quantify assessments and improve media quality. Here, cell culture media were prepared under a wide range of temperatures (40–80°C) and pH (7.6–10.0). Media quality profiles were compared using three real‐time PATs: Fourier‐transform infrared (FTIR) spectroscopy, Raman spectroscopy, and excitation‐emission matrix (EEM) spectroscopy. FTIR and Raman spectroscopies identified shifts in media quality under high preparation temperature (80°C) and at differing preparation pH which negatively impacted monoclonal antibody (mAb) production. In fed‐batch processes for production of three different mAbs, viable cell density (VCD) and cell viability were mostly unaffected under all media preparation temperatures, while titer and cell specific productivity of mAb decreased when cultured in basal and feed media prepared at 80°C. High feed preparation pH alone was tolerated but cell growth and productivity profiles deviated from the control condition. Further, charge variants (main, acidic, basic species) and glycosylation (G0F, afucosylation, and high mannose) were examined. Statistically significant differences were observed for one or more of these quality attributes with any shifts in media preparation. In this study, we demonstrated strong associations between media preparation conditions and cell growth, productivity, and product quality. The rapid evaluation of media by PAT implementation enabled more comprehensive understanding of different parameters on media quality and consequential effects on CHO cell culture. [ABSTRACT FROM AUTHOR]

Beer, with its low pH, presence of hop acids, alcohol content, and limited nutrient availability, presents a hostile environment for most bacteria. However, Levilactobacillus brevis remains a significant spoilage organism in the brewing industry. This study examines the impact of high hydrostatic pressure (HHP) on the inactivation and sublethal injury of Lb. brevis KKP 3574 in beer and wort. The results indicate that applying HHP at 400 MPa for 5 min effectively inactivates Lb. brevis, achieving up to a 7 log CFU/mL reduction in bacterial counts in beer, with no detectable sublethal injuries in beer samples. In contrast, in 10% wort, a sublethal injury level of 1.1 log CFU/mL was observed following the same HHP treatment. Furthermore, this study reveals a differential response of Lb. brevis cells depending on their growth phase; cells in the logarithmic growth phase are more susceptible to HHP, showing greater reduction in viability compared to those in the stationary phase. The survival dynamics of sublethally injured cells during refrigerated storage are also explored, with no regeneration observed in beer samples treated at pressures of 400 MPa or higher. These findings underscore the potential of HHP as a robust method for enhancing the microbiological safety and stability of beer while minimizing the risk of spoilage due to sublethally injured bacterial cells. This study provides crucial insights into optimizing HHP parameters to ensure product quality in the brewing industry. [ABSTRACT FROM AUTHOR]

Developing recombinant Saccharomyces cerevisiae strains capable of transporting and fermenting cellobiose directly is a promising strategy for second-generation ethanol production from lignocellulosic biomass. In this study, we cloned and expressed in the S. cerevisiae CEN.PK2-1C strain an intracellular β-glucosidase (SpBGL7) from Spathaspora passalidarum and co-expressed the cellobiose transporter SiHXT2.4 from Scheffersomyces illinoinensis, and two putative transporters, one from Candida tropicalis (CtCBT1 gene), and one from Meyerozyma guilliermondii (MgCBT2 gene). While all three transporters allowed cell growth on cellobiose, only the MgCBT2 permease allowed cellobiose fermentation, although cellobiose consumption was incomplete. The analysis of the β-glucosidase and transport activities revealed that the cells stopped consuming cellobiose due to a drop in the transport activity. Since ubiquitinylation of lysine residues at the N- or C-terminal domains of the permease are involved in the endocytosis and degradation of sugar transporters, we constructed truncated versions of the permease lacking lysine residues at the C-terminal domain (MgCBT2ΔC), and at both the C- and N-terminal domain (MgCBT2ΔNΔC) and co-expressed these permeases with the SpBGL7 β-glucosidase in an industrial strain. While the strain harboring the MgCBT2ΔC transporter continued to produce incomplete cellobiose fermentations as the wild-type MgCBT2 permease, the strain with the MgCBT2ΔNΔC permease was able to consume and ferment all the cellobiose present in the medium. Thus, our results highlight the importance of expressing cellobiose transporters lacking lysine at the N- and C-terminal domains for efficient cellobiose fermentation by recombinant S. cerevisiae. [ABSTRACT FROM AUTHOR]

This paper deals with the kinetics of microbial cell growth, utilization of organic substrates and methane production in upflow anaerobic filters in two and three separated stages (UAF‐2SS and UAF‐3SS) treating sanitary landfill leachates, under three temperatures (20, 27, and 34°C), fed with volumetric organic loads (VOLs) for UAF‐2SS (1.8, 2.25, 2.76, 3.45, 3.71, 4.64 kgCOD (chemical oxygen demand)/m3/d) and UAF‐3SS (1.7, 2.25, 2.44, 2.6, 3.15, 3.45, 3.5, 4.57, 4.64, 6.31, 11.61, 14.18, 17.48 kgCOD/m3/d). Kinetic parameters were obtained at temperature (20–34°C), pH (8.8–9.1), each one of three stages within the UAF‐2SS and UAF‐3SS reactors containing methanogenic bacteria (Methanococcus sp., and Methanobacterium sp.) and Clostridium sp.: Maximum substrate utilization rate (rm,s) resulted in 102 mg COD/L/h, maximum microbial cell growth rate (μm) varied 102–103 CFU (colony forming units)/mL/h, methane (CH4) production rate (rm,CH4) tended to vary 100–101 mg CH4/d and the maximum production coefficient (Y) varied 0–102 CFU/mL/h/mgCOD/L/h. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most frequent bone malignancy in humans. Previous evidence suggest that circ_0032463 is an oncogenic circular RNA (circRNA) in various cancers, including OS. However, the molecular mechanism of circ_0032463 involved in OS is still unclear. Circ_0032463, microRNA‐145‐5p (miR‐145‐5p), GDNF receptor alpha 1 (GFRA1), and Wilms tumor 1‐associated protein (WTAP) levels were determined using real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell proliferation, apoptosis, migration, invasion, and angiogenesis were analyzed using 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Western blot analysis was performed to measure matrix metalloproteinase 2 (MMP2), MMP9, GFRA1, and WTAP protein levels. Binding between miR‐145‐5p and circ_0032463 or GFRA1 was confirmed using a dual‐luciferase reporter and pull‐down assay. The biological role of circ_0032463 on OS cell growth was also analyzed using a xenograft tumor model in vivo. Methylated RNA immunoprecipitation assay validated the interaction between WTAP and circ_0032463. Circ_0032463, GFRA1, and WTAP levels were increased, and miR‐145‐5p was decreased in OS tissues and cells. Circ_0032463 deficiency might hinder OS cell proliferation, migration, invasion, angiogenesis, and promote apoptosis in vitro. Mechanically, circ_0032463 worked as a miR‐145‐5p sponge to increase GFRA1 expression. Repression of circ_0032463 knockdown on tumor cell growth was proved in vivo. Besides, N6‐methyladenosine (m6A) modification facilitates the biogenesis of circ_0032463. Taken together, m6A‐mediated biogenesis of circ_0032463 facilitates OS cell malignant biological behavior partly via regulating the miR‐145‐5p/GFRA1 axis, suggesting a promising molecular marker for OS treatment. [ABSTRACT FROM AUTHOR]

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BACKGROUND: In the perpetual struggle to manage mosquito populations, there has been increasing demand for the development of biopesticides to supplant/complement current products. The insecticidal potential of Xenorhabdus and Photorhabdus has long been recognized and is of interest for the control of important mosquitoes like Aedes albopictus which vectors over 20 different arboviruses of global public health concern. RESULTS: The larvicidal effects of cell‐free supernatants, cell growth cultures and cell mass of an extensive list of Xenorhabdus and Photorhabdus spp. was investigated. They were quite effective against Ae. albopictus causing larval mortality ranging between 52–100%. Three Photorhabdus spp. and 13 Xenorhabdus spp. release larvicidal compounds in cell‐free supernatants. Cell growth culture of all tested species exhibited larvicidal activity, except for Xenorhabdus sp. TS4. Twenty‐one Xenorhabdus and Photorhabdus bacterial cells (pellet) exhibited oral toxicity (59–91%) against exposed larvae. The effect of bacterial supernatants on the mosquito eggs were also assessed. Bacterial supernatants inhibited the hatching of mosquito eggs; when unhatched eggs were transferred to clean water, they all hatched. Using the easyPACId approach, the larvicidal compounds in bacterial supernatant were identified as fabclavine from X. szentirmaii and xencoumacin from X. nematophila (causing 98 and 70% mortality, respectively, after 48 h). Xenorhabdus cabanillasii and X. hominickii fabclavines were as effective as commercial Bacillus thuringiensis subsp. israelensis and spinosad products within 5 days post‐application (dpa). CONCLUSION: Fabclavine and xenocoumacin can be developed into novel biolarvicides, can be used as a model to synthesize other compounds or/and can be combined with other commercial biolarvicides. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are highly bioactive molecules involved not only in tissue physiology but also in the development of different human conditions, including premature aging, cardiovascular pathologies, neurological and neurodegenerative disorders, inflammatory diseases, and cancer. Among the different human tumors, cutaneous melanoma, the most aggressive and lethal form of skin cancer, is undoubtedly one of the most well-known "ROS-driven tumor", of which one of the main causes is represented by ultraviolet (UV) rays' exposure. Although the role of excessive ROS production in melanoma development in pro-tumorigenic cell fate is now well established, little is known about its contribution to the progression of the melanoma metastatic process. Increasing evidence suggests a dual role of ROS in melanoma progression: excessive ROS production may enhance cellular growth and promote therapeutic resistance, but at the same time, it can also have cytotoxic effects on cancer cells, inducing their apoptosis. In this context, the aim of the present work was to focus on the relationship between cell redox state and the signaling pathways directly involved in the metastatic processes. In addition, oxidative or antioxidant therapeutic strategies for metastatic melanoma were also reviewed and discussed. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer has become the malignant tumor with the first incidence and the second mortality among female cancers. Most female breast cancers belong to luminal-type breast cancer and HER2-positive breast cancer. These breast cancer cells all have different driving genes, which constantly promote the proliferation and metastasis of breast cancer cells. Signal transducer and activator of transcription 3 (STAT3) is an important breast cancer-related gene, which can promote the progress of breast cancer. It has been proved in clinical and basic research that over-expressed and constitutively activated STAT3 is involved in the progress, proliferation, metastasis and chemotherapy resistance of breast cancer. STAT3 is an important key target in luminal-type breast cancer and HER2-positive cancer, which has an important impact on the curative effect of related treatments. In breast cancer, the activation of STAT3 will change the spatial position of STAT3 protein and cause different phenotypic changes of breast cancer cells. In the current basic research and clinical research, small molecule inhibitors activated by targeting STAT3 can effectively treat breast cancer, and enhance the efficacy level of related treatment methods for luminal-type and HER2-positive breast cancers.

Abstract Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.

Objective To investigate the effect of calcium ions on the expression of kallikrein-4 (KLK4) and cell growth of ameloblast, and to provide an experimental basis for calcium ion promoting normal mineralization of enamel. Methods ALC cells were treated with 0, 2.0, 2.5, 3.0, and 3.5 mmol/L CaCl2 for 24 and 48 h. KLK4 expression was analyzed by qRT-PCR and Western blot analysis. The viability of ALC cells was determined by using CCK-8. AnnexinV-FITC/PI dual staining combined with flow cytometry and Hoechst 33342 staining were used to detect the ALC cell cycle and cell apoptosis. The protein expression level of glucose-regulated protein 78 (GRP78) was measured by Western blot analysis. Results After 24 h of treatment with 2.5, 3.0, and 3.5 mmol/L CaCl2, the expression of KLK4 mRNA was increased (P2, the expression of KLK4 protein was increased (P2, the expression of KLK4 mRNA and protein was increased (P2 (P2. Hoechst 33342 staining results showed that 3.0 mmol/L and 3.5 mmol/L CaCl2 may promote apoptosis in ALC cells. Flow cytometry showed that the proportion of G2/M phase cells and the apoptosis rate increased after 3.5 mmol /L CaCl2 treatment for 24 h (P2 groups. After 24 h of treatment with 3.0 mmol/L and 3.5 mmol/L CaCl2, the expression of GRP78 protein was reduced (P2, the expression of GRP78 protein was reduced (P

Survival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein‐coupled estrogen receptor‐1 (GPER1) are critical sensors of nutrient depletion and linked to poorer outcomes for females with CRC. Using a 3D spheroid model of isogenic SW48 KRAS wild‐type (WT) and G12A mutant (MT) cells grown under a restricted nutrient supply, we found that glutamine depletion inhibited cell growth in both cell lines, whereas ASNS and GPER1 expression were upregulated in KRAS MT versus WT. Estradiol decreased growth in KRAS WT but had no effect on MT cells. Selective GPER1 and ASNS inhibitors suppressed cell proliferation with increased caspase‐3 activity of MT cells under glutamine depletion condition particularly in the presence of estradiol. In a clinical colon cancer cohort from The Cancer Genome Atlas, both high GPER1 and ASNS expression were associated with poorer overall survival for females only in advanced stage tumors. These results suggest KRAS MT cells have mechanisms in place that respond to decreased nutrient supply, typically observed in advanced tumors, by increasing the expression of ASNS and GPER1 to drive cell growth. Furthermore, KRAS MT cells are resistant to the protective effects of estradiol under nutrient deplete conditions. The findings indicate that GPER1 and ASNS expression, along with the interaction between nutrient supply and KRAS mutations shed additional light on the mechanisms underlying sex differences in metabolism and growth in CRC, and have clinical implications in the precision management of KRAS mutant CRC. [ABSTRACT FROM AUTHOR]

This study sought to evaluate the influence of five macronutrients (acetate, calcium, sulfate, nitrogen, and phosphate) on the cell growth and heterologous mCherry protein production by Chlamydomonas reinhardtii. In the first step, three nitrogen (N) sources were tested (NH4NO3, NaNO3, and NH4Cl), and NH4NO3 was selected as N source for the following step, due to the best results for mCherry protein production. In the second step, a central composite design 25 was employed to evaluate the effect of the five macronutrients. Although all nutrients had effect on maximum biomass concentration, only acetate, nitrogen, and phosphate showed to influence mCherry protein production. By employing the experimental design with small‐scale culture in multiplates and multivariable regression, it was possible to achieve 12 % increase for recombinant protein production. [ABSTRACT FROM AUTHOR]

Despite significant research efforts in the continuum modeling of biological growth, certain aspects have been overlooked. For instance, numerous investigations have examined the influence of morphogenetic cell behaviors, like division and intercalation, on the mechanical response of passive (non-growing) tissues. Yet, their impact on active growth dynamics remains inadequately explored. A key reason for this inadequacy stems from challenges in the continuum treatment of cell-level processes. While some coarse-grained models have been proposed to address these shortcomings, a focus on cell division and cell expansion has been missing, rendering them unusable when it comes to modeling growth. Moreover, existing studies are limited to two-dimensional tissues and are yet to be formally extended to three-dimensional multicellular systems. To address these limitations, we here present a generalized multiscale model for three-dimensional aggregates that accounts for complex morphogenetic movements that include division, expansion, and intercalation. The proposed continuum theory thus allows for a comprehensive exploration into the growth and dissipation mechanics of proliferating aggregates, such as spheroids and organoids. [ABSTRACT FROM AUTHOR]

Oleaginous microalgae have gained increasing attention as an alternative feedstock for biodiesel production due to the increasing demand of fuel, climate change, and global warming. This study aimed to isolate and screen robust microalgal strains from hot springs for cultivation in subtropical and tropical areas. The newly isolated oleaginous microalgae were cultivated at 30, 35 and 40 °C. Among mesophilic and thermophilic strains tested, Chlamydomonas sp. HP59 is considered the most robust strain as it showed high cell growth in a broad range of temperatures (30 - 40 °C), with the maximum dried cell weight at 40 °C. Un-optimal temperatures for cell growth did improve lipid content by 2 - 4 folds. To increase lipid production, the 2-stage cultivation, in which nitrogen-rich was applied to promote cell growth in the 1st stage and nitrogen-limitation was applied to stimulate lipid accumulation in the 2nd stage, was performed. The high temperature combined with nitrogen-limitation did improve lipid production by all microalgae. With this strategy, Chlamydomonas sp. HP59 showed the highest dried cell weight of 4.33 g/L and lipid production of 1.72 g/L. This study has shown the potential use of the newly isolated oleaginous microalgae from hot springs to be cultivated at high temperatures and under nitrogen-limited conditions for the production of biodiesel feedstocks. [ABSTRACT FROM AUTHOR]

The mostly aggressive and extremely malignant type of central nervous system is Glioblastoma (GBM), which is characterized by an extremely short average survival time of lesser than 16 months. The primary cause of this phenomenon can be attributed to the extensively altered genome of GBM, which is characterized by the dysregulation of numerous critical signaling pathways and epigenetics regulations associated with proliferation, cellular growth, survival, and apoptosis. In light of this, different genetic alterations in critical signaling pathways and various epigenetics regulation mechanisms are associated with GBM and identified as distinguishing markers. Such GBM prognostic alterations are identified in PI3K/AKT, p53, RTK, RAS, RB, STAT3 and ZIP4 signaling pathways, metabolic pathway (IDH1/2), as well as alterations in epigenetic regulation genes (MGMT, CDKN2A-p16INK4aCDKN2B-p15INK4b). The exploration of innovative diagnostic and therapeutic approaches that specifically target these pathways is utmost importance to enhance the future medication for GBM. This study provides a comprehensive overview of dysregulated epigenetic mechanisms and signaling pathways due to mutations, methylation, and copy number alterations of in critical genes in GBM with prevalence and emphasizing their significance. [ABSTRACT FROM AUTHOR]

This study explored the effects of β-1,3/1,6-glucan derived from Saccharomyces cerevisiae cell walls on the growth, survival, and physiological responses of post-larvae (PL) of M. rosenbergii. Over a 3-week period, larvae were fed a formulated egg custard diet containing varying amounts of β-glucan. The findings revealed that incorporating β-glucan into the diet had a substantial positive impact. The inclusion of β-glucans significantly enhanced survival (59.14% for the PL fed 0.2% β-glucan versus 46.58% for the control; p < 0.05), promoted growth (13.58 mg wet weight for the PL fed 0.2% β-glucan versus 9.53 mg for the PL fed the control diet; p < 0.05), and accelerated the time to metamorphosis (26.67 days for the PL fed 0.2% β-glucan versus 28.0 days for the PL fed the control diet). As the amount of β-glucan in the diet increased, larval growth performance consistently improved. The group receiving 0.2% β-glucan exhibited the highest performance in terms of wet and dry weight, total length, and mean production of PL. Furthermore, the study assessed the influence of β-glucan supplementation on larval tolerance to hypersaline stress. Although the differences were not statistically significant, the addition of β-glucan resulted in incremental improvements in the ability of larvae to withstand hypersaline conditions. In conclusion, the dietary supplement containing 0.2% β-glucan exhibited the highest performance among the inclusion levels tested. Further investigation is recommended to determine the nutritional and physiological effects of β-glucan supplementation under salinity stress conditions. [ABSTRACT FROM AUTHOR]

Recurrent spontaneous abortions (RSA) affect reproductive health and increase the risk of subsequent abortions. to investigate the role of KISS-1/GPR-54 signaling in RSA progression. Villus tissue was collected from Rsa patients, and human trophoblastic HTR-8/SVneo cells were used. KISS-1 and GRP54 levels were detected using RT-qPCR and immunohistochemistry. Western blotting was performed to analyze ZO-1 and ZEB1 levels. cell proliferation was determined via ccK-8 and cell clone formation assays. transwell assays were performed to assess cell migration and invasion abilities. KISS-1 was down-regulated in the villus tissues of RSA patients. KISS-1 overexpression dramatically inhibited trophoblast proliferation, migration, and invasion. Mechanistically, ZEB1 expression was down-regulated, whereas ZO-1 expression was up-regulated, after Kiss-1 overexpression. GPR54 silencing neutralized the effect of KISS-1 in HTR-8/SVneo cells. additionally, Kiss-1 overexpression inactivated the PI3K/AKT signaling pathway through GRP54. the KISS-1/GPR-54 signaling axis regulates RSA progression by regulating the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

One new lathyrane-type diterpenoid, euphlathin A (1), and 11 known analogues (2–12), were isolated from the fruits of Euphorbia lathyris. Their structures were elucidated by spectroscopic data. The absolute configurations of 1 were established by single-crystal X-ray crystallography. All diterpenoids (1–12) were evaluated for antiproliferative activity against the human hypertrophic scar (HTS) cells. Compound 1 exhibited significantly against HTS cells growth with an IC50 value of 6.33 μM. Morphological features of apoptosis were evaluated in 1-treated HTS cells. Wound healing assays indicated that 1 significantly inhibited the migration of HTS at 24 h and 48 h. Compound 1 effectively induced apoptosis of HTS, which was associated with G2/M or S phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 1 significantly induced HTS cell apoptosis in a dose-dependent manner. Overall, euphlathin A (1) has the potential to be a therapeutic agent for the treatment of hyperplastic scar therapy. [ABSTRACT FROM AUTHOR]

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β‐19α‐trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT‐qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M‐TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells. Rubus imperialis (Rosaceae) is a medicinal plant. However, it revealed cellular/genetic toxicity. Being 2β,3β‐19α‐trihydroxyursolic acid (2B) is a major compound of this plant, but its biosafety was not investigated. Therefore, (2B) was tested by cytogenotoxic endpoints in HepG2/C3A cells. The compound did not produce any of decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT‐qPCR analysis revealed downregulation of CYP3A4 (metabolism), M‐TOR (cell death), and CDKN1A (cell cycle) genes. [ABSTRACT FROM AUTHOR]

Yeast is one of the co-products of ethanol plants, which can be used as a nutritional supplement in animal feed due to its high protein content. Given the importance of yeast contribution to the nutritional properties of DDG (dried distillers’ grains), the aim of this study was to assess how different levels of aeration affect the biomass production and the quality of yeast providing new insights into yeast production, offering an alternative source of income for the corn ethanol industry. For this purpose, yeasts were grown in a fed-batch process, and different concentrations of aeration in the medium were tested, namely 0.5, 1.0, and 1.5 volume of air per volume of wort per minute (v v−1 min−1). At the end of the cellular biomass production process, yeasts grown with 0.5 (v v−1 min−1) aeration in the reactor showed higher biomass formation (19.86 g L−1), cellular yield (g g−1), and a lower formation of succinic acid (0.70 g L−1) and acetic acid (0.11 g L−1). Aeration influenced an increase of 1.0% in the protein content in yeast. In conclusion, lower levels of aeration in the yeast production process enables more efficient sugar utilization for biomass formation and is a potential strategy to increase the protein content and the commercial value of DDG.

Abstract Background Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. Methods The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. Results CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). Conclusions CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

Gluconobacter oxydans is an important Gram-negative industrial microorganism that produces vitamin C and other products due to its efficient membrane-bound dehydrogenase system. Its incomplete oxidation system has many crucial industrial applications. However, it also leads to slow growth and low biomass, requiring further metabolic modification for balancing the cell growth and incomplete oxidation process. As a non-model strain, G. oxydans lacks efficient genome editing tools and cannot perform rapid multi-gene editing and complex metabolic network regulation. In the last 15 years, our laboratory attempted to deploy multiple CRISPR/Cas systems in different G. oxydans strains and found none of them as functional. In this study, Cpf1-based or dCpf1-based CRISPRi was constructed to explore the targeted binding ability of Cpf1, while Cpf1–FokI was deployed to study its nuclease activity. A study on Cpf1 found that the CRISPR/Cpf1 system could locate the target genes in G. oxydans but lacked the nuclease cleavage activity. Therefore, the CRISPR/Cpf1–FokI system based on FokI nuclease was constructed. Single-gene knockout with efficiency up to 100% and double-gene iterative editing were achieved in G. oxydans. Using this system, AcrVA6, the anti-CRISPR protein of G. oxydans was discovered for the first time, and efficient genome editing was realized.

AbstractAcute promyelocytic leukemia (APL) is marked by a block at the promyelocyte stage. Treatments like ATRA and ATO face resistance and relapse issues. Plastrum testudinis, a traditional Chinese medicine, may offer therapeutic potential. This study investigated xtr-miR-22-3p from P. testudinis for treating APL. High expression of xtr-miR-22-3p was confirmed, with target prediction indicating interactions with key genes, including PML. xtr-miR-22-3p reduced HL-60 leukemia cell growth, altered the cell cycle, and selectively inhibited HL-60 proliferation while promoting BMSC growth, suggesting its potential as a targeted APL therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The intestine is a barrier resisting various stress responses. Intrauterine growth restriction (IUGR) can cause damage to the intestinal barrier via destroying the balance of intestinal epithelial cells' proliferation and apoptosis. Bacillus subtilis has been reported to regulate intestinal epithelial cells' proliferation and apoptosis. Thus, the purpose of this study was to determine if B. subtilis could regulate intestinal epithelial cells' proliferation and apoptosis in intrauterine growth restriction suckling piglets. RESULTS: Compared with the normal birth weight group, the IUGR group showed greater mean optical density values of Ki‐67‐positive cells in the ileal crypt (P < 0.05). IUGR resulted in higher ability of proliferation and apoptosis of intestinal epithelial cells, by upregulation of the messenger RNA (mRNA) or proteins expression of leucine rich repeat containing G protein coupled receptor 5, Caspase‐3, Caspase‐7, β‐catenin, cyclinD1, B‐cell lymphoma‐2 associated agonist of cell death, and BCL2 associated X (P < 0.05), and downregulation of the mRNA or protein expression of B‐cell lymphoma‐2 and B‐cell lymphoma‐2‐like 1 (P < 0.05). However, B. subtilis supplementation decreased the mRNA or proteins expression of leucine rich repeat containing G protein coupled receptor 5, SPARC related modular calcium binding 2, tumor necrosis factor receptor superfamily member 19, cyclinD1, Caspase‐7, β‐catenin, B‐cell lymphoma‐2 associated agonist of cell death, and Caspase‐3 (P < 0.05), and increased the mRNA expression of B‐cell lymphoma‐2 (P < 0.05). CONCLUSION: IUGR led to excessive apoptosis of intestinal epithelial cells, which induced compensatory proliferation. However, B. subtilis treatment prevented intestinal epithelial cells of IUGR suckling piglets from excessive apoptosis. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This study investigates the potential of incorporating akermanite and hardystonite nanoparticles (NPs) into commercially available zinc phosphate cement. Akermanite and hardystonite NPs were synthesized through a mechanical route and characterized using X‐ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The NPs were then added to the cement at a concentration of 5 wt%, and the physical and biological properties of the resulting composite were evaluated. The results showed that the incorporation of NPs led to a significant reduction in porosity (from 12.4% to 5.6%) and a notable improvement in compressive strength (from 90 to 120 MPa) compared to the control group. MTT assay revealed that the cement containing NPs exhibited no significant toxicity and even promoted cell growth and proliferation. Specifically, cell viability increased by 15%, and cell proliferation rate increased by 20% compared to the control group. These findings suggest that the designed cement has suitable mechanical and biological properties, making it a promising material for dental and orthopedic applications. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the "GATOR" supercomplex. The nucleotide state of RagA/B controls the lysosomal association of GATOR, in a fashion competitively antagonized by the N terminus of the amino acid transporter SLC38A9. Targeting of Ragulator to the surface of mitochondria is sufficient to relocalize the Rags and GATOR to this organelle, but not to enable the nutrient-regulated recruitment of mTORC1 to mitochondria. Thus, our results reveal that the Rag-Ragulator complex is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway and underscore that mTORC1 activation requires signal transduction on the lysosomal surface. [ABSTRACT FROM AUTHOR]