GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway.

Sepsis is a systemic inflammatory response syndrome triggered by infection, presenting with symptoms such as fever, increased heart rate, and low blood pressure. In severe cases, it can lead to multiple organ dysfunction, posing a life-threatening risk. Sepsis-induced cardiomyopathy (SIC) is a critical factor in the poor prognosis of septic patients, leading to myocardial dysfunction characterized by cell death, inflammation, and diminished cardiac function. Ferroptosis, an iron-dependent form of programmed cell death, is a key mechanism causing cardiomyocyte damage in SIC. Growth differentiation factor 15 (GDF15), a member of the TGF-ß superfamily, is associated with various cardiovascular diseases and can inhibit oxidative stress, reduce reactive oxygen species (ROS), and suppress ferroptosis. Elevated serum GDF15 levels in sepsis are correlated with organ injuries, suggesting its potential as a therapeutic target. However, its role and mechanisms in SIC remain unclear. Glutathione peroxidase 4 (GPX4), the only enzyme capable of reducing lipid peroxides within cells, protects cells by reducing lipid peroxidation levels and inhibiting ferroptosis. Investigating the regulatory factors of GPX4 may provide a theoretical basis for SIC treatment. In this study, a mouse SIC model revealed that elevated GDF15 exerts a protective effect. Antagonizing GDF15 exacerbates myocardial damage. Through transcriptomic analysis and other methods, we confirmed that GDF15 inhibits the expression of SOCS1 by activating the ALK5-SMAD2/3 pathway, thereby activates the JAK2/STAT3 pathway, promotes the transcription of GPX4, inhibits ferroptosis in cardiomyocytes, and plays a myocardial protective role in SIC.

Noviherbaspirillum album sp. nov., an airborne bacteria isolated from an urban area of Beijing, China.

A Gram-negative, ellipsoidal to short-rod-shaped, motile bacterium was isolated from Beijing's urban air. The isolate exhibited the closest kinship with Noviherbaspirillum aerium 122213-3T, exhibiting 98.4 % 16S rRNA gene sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that it clustered closely with N. aerium 122213-3T, thus forming a distinct phylogenetic lineage within the genus Noviherbaspirillum. The average nucleotide identity and digital DNA-DNA hybridization values between strain I16B-00201T and N. aerium 122213-3T were 84.6 and 29.4 %, respectively. The respiratory ubiquinone was ubiquinone 8. The major fatty acids (>10 %) were summed feature 3 (C16:1ω6c/C16:1ω7c, 43.3 %), summed feature 8 (C18:1ω7c/C18:1ω6c, 15.9 %) and C12:0 (11.0 %). The polyamine profile showed putrescine as the predominant compound. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, unknown lipids and unknown phosphatidylaminolipids. The phenotypic, phylogenetic and chemotaxonomic results consistently supported that strain I16B-00201T represented a novel species of the genus Noviherbaspirillum, for which the name Noviherbaspirillum album sp. nov. is proposed, with I16B-00201T (=CPCC 100848T=KCTC 52095T) designated as the type strain. Its DNA G+C content is 59.4 mol%. Pan-genome analysis indicated that some Noviherbaspirillum species possess diverse nitrogen and aromatic compound metabolism pathways, suggesting their potential value in pollutant treatment.

Glycogen synthase kinase-3ß: A multifaceted player in ischemia-reperfusion injury and its therapeutic prospects.

Ischemia-reperfusion injury (IRI) results in irreversible metabolic dysfunction and structural damage to tissues or organs, posing a formidable challenge in the field of organ implantation, cardiothoracic surgery, and general surgery. Glycogen synthase kinase-3ß (GSK-3ß) a multifunctional serine/threonine kinase, is involved in a variety of biological processes, including cell proliferation, apoptosis, and immune response. Phosphorylation of its tyrosine 216 and serine 9 sites positively and negatively regulates the activation and inactivation of the enzyme. Significantly, inhibition or inactivation of GSK-3ß provides protection against IRI, making it a viable target for drug development. Though numerous GSK-3ß inhibitors have been identified to date, the development of therapeutic treatments remains a considerable distance away. In light of this, this review summarizes the complicated network of GSK-3ß roles in IRI. First, we provide an overview of GSK-3ß's basic background. Subsequently, we briefly review the pathological mechanisms of GSK-3ß in accelerating IRI, and highlight the latest progress of GSK-3ß in multiorgan IRI, encompassing heart, brain, kidney, liver, and intestine. Finally, we discuss the current development of GSK-3ß inhibitors in various organ IRI, offering a thorough and insightful reference for GSK-3ß as a potential target for future IRI therapy.

T Cell-Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1.

Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell-derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2'3' cyclic GMP-AMP (cGAMP) and activates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS-STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

Tetrahydrocurcumin ameliorates postinfarction cardiac dysfunction and remodeling by inhibiting oxidative stress and preserving mitochondrial function via SIRT3 signaling pathway.

BACKGROUND: Myocardial infarction (MI) often leads to sudden cardiac death. Persistent myocardial ischemia increases oxidative stress and impairs mitochondrial function, contributing significantly to postinfarction cardiac dysfunction and remodeling, and the subsequent progression to heart failure (HF). Tetrahydrocurcumin (THC), isolated from the rhizome of turmeric, has antioxidant properties and has been shown to protect against cardiovascular diseases. However, its effects on HF after MI are poorly understood. PURPOSE: The objective was the investigation of the pharmacological effects of THC and its associated mechanisms in the pathogenesis of HF after MI. METHODS: A total of 120 mice (C57BL/6, male) were used for the in vivo experiments. An MI mouse model was created by permanent ligation of the left anterior descending coronary artery. The mice received oral dose of THC at 120 mg/kg/d and the effects on MI-induced myocardial injury were evaluated by assessment of cardiac function, histopathology, myocardial oxidative levels, and mitochondrial function. Molecular mechanisms were investigated by intraperitoneal injection of 50 mg/kg of the SIRT3 selective inhibitor 3-TYP. Meanwhile, mouse neonatal cardiomyocytes were isolated and cultured in a hypoxic incubator to verify the effects of THC in vitro. Lastly, SIRT3 and Nrf2 were silenced using siRNAs to further explore the regulatory mechanism of key molecules in this process. RESULTS: The mouse hearts showed significant impairment in systolic function after MI, together with enlarged infarct size, increased myocardial fibrosis, cardiac hypertrophy, and apoptosis of cardiomyocytes. A significant reversal of these changes was seen after treatment with THC. Moreover, THC markedly reduced reactive oxygen species generation and protected mitochondrial function, thus mitigating oxidative stress in the post-MI myocardium. Mechanistically, THC counteracted reduced Nrf2 nuclear accumulation and SIRT3 signaling in the MI mice while inhibition of Nrf2 or SIRT3 reversed the effects of THC. Cell experiments showed that Nrf2 silencing markedly reduced SIRT3 levels and deacetylation activity while inhibition of SIRT3 signaling had little impact on Nrf2 expression. CONCLUSION: This is the first demonstration that THC protects against the effects of MI. THC reduced both oxidative stress and mitochondrial damage by regulating Nrf2-SIRT3 signaling. The results suggest the potential of THC in treating myocardial ischemic diseases.

Extra-anatomic revascularization and a new cannulation strategy for preoperative cerebral malperfusion due to severe stenosis or occlusion of supra-aortic branch vessels in acute type A aortic dissection.

Objectives: Acute type A aortic dissection (ATAAD) with severe stenosis or occlusion of the true lumen of aortic arch branch vessels often leads to an increased incidence of severe postsurgical neurological complications and mortality rate. In this study, we aimed to introduce our institutional extra-anatomic revascularization and cannulation strategy with improved postoperative outcomes for better management of patients with cerebral malperfusion in the setting of ATAAD. Methods: Twenty-eight patients with ATAAD complicated by severe stenosis or occlusion of the aortic arch branch vessels, as noted on combined computed tomography angiography of the aorta and craniocervical artery, between January 2021 and June 2022 were included in this study. Basic patient characteristics, surgical procedures, hospitalization stays, and early follow-up results were analyzed. Results: The median follow-up duration was 16.5 months (interquartile range: 11.5-20.5), with a 100% completion rate. The 30-day mortality rates was 7.1% (2/28 patients); two patients had multiple cerebral infarctions on preoperative computed tomography and persistent coma. Postoperative transient neurological dysfunction occurred in 10.7% (3/28) of the patients, and no new permanent neurological dysfunction occurred. Of all the patients, 3.6% (1/28) had novel acute renal failure. No other deaths, secondary surgeries, or serious complications occurred during the early follow-up period. Conclusions: Use of extra-anatomic revascularization and a new cannulation strategy before cardiopulmonary bypass is safe and feasible and may reduce the high incidence of postoperative neurological complications in patients with ATAAD and cerebral malperfusion.

The mediating role of green innovation and green culture in the relationship between green human resource management and environmental performance.

There is evidence in the literature that green HRM practices improve environmental profitability. On the other hand, existing research has failed to explain how GHRM can support the development of a green culture and green innovation influence the firm's environmental performance and long-term growth. This study investigates the relationship between GHRM, green culture, green innovation, and a firm's environmental performance. In addition, the study examines the mediating role of green culture and green innovation in the relationship between GHRM and environmental performance. This research conducts a large-scale study of 290 employees from Manufacturing firms in Malaysia. The research results provide managers with a better knowledge of how GHRM helps develop sustainable culture and green innovation and how these elements contribute to the improvement of environmental performance inside the organization. This study also makes a significant contribution in terms of novelty and research relevance by demonstrating that green culture and green innovation positively mediate the relationship between GHRM and environmental performance in a sustainable manner. Managers will understand the GHRM required to develop an ecologically conscious culture and promote green innovation among environmentally conscious employees. Finally, we highlighted the importance of this study for top management in the sense of mediating the role of green culture and green innovation and the consequences for future generations of responsible managers who will acquire this knowledge.

Early essential newborn care is associated with increased breastfeeding: a quasi-experimental study from Sichuan Province of Western China.

BACKGROUND: Breastfeeding is critical to promote maternal and child health. China has set national targets to further improve the exclusive breastfeeding rate. We aimed to examine associations between the provision of early essential newborn care (EENC) and breastfeeding outcomes among full term vaginally delivered neonates in the first 6 months of life. METHODS: We conducted a quasi-experimental study in eight maternal and children's hospitals in Mianyang City and Deyang City in Sichuan Province of western China. Four hospitals were randomly selected as the intervention group with the implementation of EENC while others as the control group receiving routine care. We assessed effects of EENC on breastfeeding initiation time, duration of first-time breastfeeding, and exclusive breastfeeding rates up to 6 months of age. Data were collected after delivery, at hospital discharge, 1 month, 3 months, and 6 months post birth in the baseline phase from May to June 2017 and post-EENC phase from October to December 2017. We performed univariate analyses to ascertain differences between the two groups, and difference in difference (DID) models to explore the net effects. RESULTS: Of the 1349 enrolled mother and newborn pairs in our study, 1131 (83.9%) were followed up at 1 month of age, 1075 (79.7%) at 3 months, and 981 (72.7%) at 6 months. EENC was associated with earlier median time to initiate breastfeeding (25 min vs. 33 min, P <  0.01), an increased chance of successful first-time breastfeeding (OR 5.53; 95% CI 2.69, 11.40), longer duration of skin to skin contact (SSC) (21.53 min; 95% CI 18.17, 24.89) and longer duration of the first breastfeed (4.16 min; 95% CI 2.10, 6.22), and an increased likelihood of being exclusively breastfed at discharge (74.5% vs. 55.0%, P <  0.001), 3 months (OR 3.20; 95% CI 1.01, 10.15), and 6 months (OR 4.91; 95% CI 1.71, 14.13) of age. CONCLUSIONS: EENC enhances breastfeeding initiation and increases exclusive breastfeeding at 6 months of age. Our evidence suggests that nationwide scale up of EENC would increase the exclusive breastfeeding rate in the first 6 months of life.

Isolation, in vitro culture and identification of a new type of mesenchymal stem cell derived from fetal bovine lung tissues.

Lung­derived mesenchymal stem cells (LMSCs) are considered to be important in lung tissue repair and regenerative processes. However, the biological characteristics and differentiation potential of LMSCs remain to be elucidated. In the present study, fetal lung­derived mesenchymal stem cells (FLMSCs) were isolated from fetal bovine lung tissues by collagenase digestion. The in vitro culture conditions were optimized and stabilized and the self­renewal ability and differentiation potential were evaluated. The results demonstrated that the FLMSCs were morphologically consistent with fibroblasts, were able to be cultured and passaged for at least 33 passages and the cell morphology and proliferative ability were stable during the first 10 passages. In addition, FLMSCs were found to express CD29, CD44, CD73 and CD166, however, they did not express hematopoietic cell specific markers, including CD34, CD45 and BOLA­DRα. The growth kinetics of FLMSCs consisted of a lag phase, a logarithmic phase and a plateau phase, and as the passages increased, the proliferative ability of cells gradually decreased. The majority of FLMSCs were in G0/G1 phase. Following osteogenic induction, FLMSCs were positive for the expression of osteopontin and collagen type I α2. Following neurogenic differentiation, the cells were morphologically consistent with neuronal cells and positive for microtubule­associated protein 2 and nestin expression. It was concluded that the isolated FLMSCs exhibited typical characteristics of mesenchymal stem cells and that the culture conditions were suitable for their proliferation and the maintenance of stemness. The present study illustrated the potential application of lung tissue as an adult stem cell source for regenerative therapies.

[Qilin pills combined with bromocriptine for idiopathic hyperprolactinemic oligoasthenozoospermia].

OBJECTIVE: To observe the therapeutic effect of Qilin Pills combined with bromocriptine on idiopathic hyperprolactinemic (HPRL) oligoasthenospermia. METHODS: We conducted a randomized controlled study on 40 cases of idiopathic HPRL oligoasthenospermia, who were equally assigned to a trial group and a control group to be treated with Qilin Pills (6 g tid) combined with bromocriptine and bromocriptine alone, respectively, both for a course of 12 weeks. Then we observed the changes in the semen volume, sperm concentration, sperm motility and the levels of serum prolactin and testosterone, and compared the therapeutic results between the two groups before and after medication. RESULTS: Compared with the parameters before medication, both the trial and the control group showed significant improvement after treatment in sperm concentration ([11.60 +/- 3.90] x 10(6)/ml vs [28.10 +/- 13.50] x 10(6)/ml and [12.03 +/- 4.10] x 10(6)/ml vs [18.85 +/- 8.50] x 10(6)/ml), the percentage of grade a sperm ([8.75 +/- 6.65]% vs [24.35 +/- 13.25 ]% and [8.70 +/- 6.70] % vs [19.65 +/- 10.05]%), the percentage of grade a + b sperm ( [28.45 +/- 11.35]% vs [45.80 +/- 16.55]% and [27.65 +/- 10.65]% vs [35.66 +/-13.25]%), and sperm motility ([38.22 +/- 16.35]% vs [60.05 +/- 20.65]% and [37.25 +/- 15.75 ]% vs [52.65 +/- 18.25 ]%) (all P<0.01). No significant differences were found in semen volume (P>0.05). The serum prolactin levels were significantly decreased in the trial and control groups ([152.00 +/- 22.32] and [160.45 +/- 26.65] mIU/L), as compared with premedication ([482.25 +/- 65.32] and [477.32 +/- 60.25] mIU/L) (P<0.01), while the serum testosterone levels were remarkably higher ([16.35 +/- 5.52] and [11.15 +/- 4.65] nmol/L) than before treatment ([3.75 +/- 1.10] and [4.05 +/- 1.30] nmol/L) (P<0.01). There were no statistically significant differences in the serum prolactin and testosterone levels between the two groups after treatment (P>0.05). CONCLUSION: Qilin Pills combined with bromocriptine have a significantly better efficacy than bromocriptine alone in the treatment of idiopathic HPRL oligoasthenospermia.

[Regulatory effect of GDNF on the proliferation and differentiation of mammalian spermatogonial stem cells].

The glial cell-derived neurotrophic factor (GDNF) is a member of the transforming growth factor beta (Tgf-beta) superfamily, which is produced by Sertoli cells and plays an important role in the proliferation and differentiation of spermatogonial stem cells (SSC). The addition of proper amount of GDNF to the culture media can promote SSC proliferation in vitro. Besides, GDNF regulates the self-renewal and differentiation of SSCs through various signaling pathways. This review focuses on the effects of GDNF on the proliferation and differentiation of mammalian SSCs and GDNF-mediated signaling pathways.