Mitochondrial ribosomal protein L12 potentiates hepatocellular carcinoma by regulating mitochondrial biogenesis and metabolic reprogramming.

BACKGROUND: Mitochondrial dysfunction and metabolic reprogramming are key features of hepatocellular carcinoma (HCC). Despite its significance, the precise underlying mechanism behind these processes has not been fully elucidated. The latest investigations, along with our previous discoveries, have substantiated the significant role of mitochondrial ribosomal protein L12 (MRPL12), a newly identified gene involved in mitochondrial transcription regulation, in the modulation of mitochondrial metabolism. Nevertheless, the role of MRPL12 in tumorigenesis has yet to be investigated. METHODS: The expression of MRPL12 in HCC was assessed using an online database. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) were employed to determine the expression of MRPL12 in HCC tissues, patient-derived organoid (PDO), and cell lines. The correlation between MRPL12 expression and clinicopathological features, as well as prognosis, was examined using tissue microarray analysis. An in vivo subcutaneous tumor xenograft model, gene knockdown or overexpression assay, chromatin immunoprecipitation (ChIP) assay, Seahorse XF96 assay, and cell function assay were employed to investigate the biological function and potential molecular mechanism of MRPL12 in HCC. RESULTS: A significant upregulation of MRPL12 was observed in HCC cells, PDO and patient tissues, which correlated with advanced tumor stage, higher grade and poor prognosis. MRPL12 overexpression promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenicity in vivo, whereas MRPL12 knockdown showed the opposite effect. MRPL12 knockdown also inhibited the capacity of organoids proliferation capacity. Furthermore, MRPL12 was found to be crucial for maintaining mitochondrial homeostasis. Both gain and loss-of-function experiments targeting MRPL12 in HCC cells altered oxidative phosphorylation (OXPHOS) and mitochondrial DNA content. Notably, suppression of OXPHOS effectively mitigates the tumor-promoting effect attributed to MRPL12 overexpression, implying the involvement of MRPL12 in HCC through the modulation of mitochondrial metabolism. Besides, Yin Yang 1 (YY1) was identified as a transcription factor responsible for regulating MRPL12, while the PI3K/mTOR pathway was found to act as an upstream regulator of YY1. MRPL12 knockdown attenuated the YY1 overexpression or PI3K/mTOR activation-induced malignant phenotype in HCC cells. CONCLUSION: Our findings provide compelling evidence that MRPL12 is implicated in driving the malignant phenotype of HCC via regulating mitochondrial metabolism. Moreover, the aberrant expression of MRPL12 in HCC is mediated by the upstream PI3K/mTOR/YY1 pathway. These results highlight the potential of targeting MRPL12 as a promising therapeutic strategy for the treatment of HCC.

Delivery of Telehealth Complementary and Integrated Health Interventions Improves Mental Health and Overall Wellness to Broaden Veterans' Access to Care.

Background: Complementary and integrative health (CIH) interventions show promise in improving overall wellness and engaging Veterans at risk of suicide. Methods: An intensive 4-week telehealth CIH intervention programming was delivered motivated by the COVID-19 pandemic, and outcomes were measured pre-post program completion. Results: With 93% program completion (121 Veterans), significant reduction in depression and post-traumatic stress disorder symptoms were observed pre-post telehealth CIH programing, but not in sleep quality. Improvements in pain symptoms, and stress management skills were observed in Veterans at risk of suicide. Discussion: Telehealth CIH interventions show promise in improving mental health symptoms among at-risk Veterans, with great potential to broaden access to care toward suicide prevention.

Correlation Analysis and Application of Respiratory and Lung Diseases in Pediatrics of Traditional Chinese Medicine Based on Factor Analysis Method.

Many scholars have studied the influencing factors of children's lung infection, whether it is the region or the environment, or the living air quality of the mother during pregnancy. Western medicine is the most frequently used medicine, but Chinese medicine has more remarkable characteristics in treating children's lung diseases. For viral invasive diseases, people often use antibiotics to treat them. Children's lung conditions are too fragile, and taking antibiotics will lead to the damage of Staphylococcus in the lungs, resulting in pulmonary respiratory insufficiency. Although the conditioning time of traditional Chinese medicine is longer than that of western medicine, traditional Chinese medicine will not cause secondary damage to the lungs. In this paper, we introduce factor analysis and principal component analysis and compare the performance of the three analysis methods by using data such as cure rate, improvement rate, mortality rate, and drug taking frequency as evaluation indexes. In the model comparison, the accuracy rate of factor analysis method is over 97%, while the error rate is below 5%. Compared with the other two analysis methods, this method has a better application effect. Finally, we compare the comprehensive scores of eigenvalues of the three analysis methods. From 2016 to 2021, the comprehensive scores of factor analysis gradually increased.

Characterization of the complete chloroplast genome of Lonicera tangutica (Caprifoliaceae), an ornamental and medicinal plant in China.

In the present study, the complete chloroplast genome of Lonicera tangutica is presented and characterized for the first time. The complete chloroplast genome was 156,121 bp in length, including 23,899 bp inverted repeat (IR) regions, an 89,466 bp large single-copy (LSC) region, and an 18,851 bp small single-copy (SSC) region. A total of 129 genes, including 37 tRNA genes, eight rRNA genes, and 84 protein-coding genes, were annotated, and the overall GC content of the chloroplast genome was 38.35%. Two introns in the ycf3 gene and a single intron in another gene were detected. Maximum-likelihood phylogenetic analysis indicated that L. tangutica has a very close evolutionary relationship with Lonicera praeflorens, Lonicera hispida, Lonicera fragrantissima, and Lonicera stephanocarpa. These results are valuable for studying the evolution and genetic diversity of L. tangutica.

Pilot evaluation of horticultural therapy in improving overall wellness in veterans with history of suicidality.

OBJECTIVES: Novel approaches to mental health and suicide prevention are lacking. Converging evidence has shown the effectiveness of horticultural therapy (HT) in improving mental health symptoms, but whether it would reduce suicide risk and contributing risk factors is unknown. DESIGN: Using a cohort model, HT was delivered 3.5 h over four weekly, sessions administered by a registered horticultural therapist to veterans with history of suicide ideation or attempt who felt isolated and experienced ongoing environmental stressors with interest in learning new coping strategies. SETTING: HT delivery occurred in an urban garden, through a community partnership between the VA (Veterans Administration) and the New York Botanical Garden. Guided by principles of biophilia, participating veterans took part in nature walks, self-reflection and journaling, and planting activities. OUTCOME MEASURES: Stress, mood, pain, and social isolation levels were measured weekly pre-post HT sessions using thermometer scales, with concordant validity to validated clinical instruments. RESULTS: Of the 20 men and women with a history of suicide attempts/ideation, HT demonstrated immediate improvements after each session across all symptom domains in magnitude of reduction in stress, pain, mood, and loneliness. The effect sizes were in medium to large range (Cohen's d>.5). Additionally, a single HT session showed a sustained effect over subsequent 2-to-4 weeks as observed by the significantly decreased pre-session thermometer scores in subsequent weeks. Reductions in mood symptoms correlated with decline in suicidal ideation (rs = 0.63). CONCLUSION: HT intervention maybe a promising therapeutic modality for improving overall wellness in suicide prevention in at-risk veteran populations.

Effectiveness of Complementary and Integrative Approaches in Promoting Engagement and Overall Wellness Toward Suicide Prevention in Veterans.

Objective: Suicide is a major public health problem, specifically among U.S. veterans, who do not consistently engage in mental health services, often citing stigma as a barrier. Complementary and Integrative Health (CIH) interventions are promising alternatives in promoting patient engagement and further, they may play a critical role in transitioning people into mental health care. Toward this goal, the Resilience and Wellness Center (RWC) was developed to break through the stigma barrier by addressing risk factors of suicide through multimodal CIH interventions via cohort design, promoting social connectedness and accountability among participants. Design: This is a program evaluation study at a large urban VA medical center, where assessments were evaluated from pre- to post-program completion to determine the effectiveness of an intensive multimodal CIH 4-week group outpatient intervention for suicide prevention. Outcome measures: Primary outcomes measured included group connectedness, severity of depression and hopelessness symptoms, suicidal ideation, sleep quality, and diet. Secondary outcomes included measures of post-traumatic stress disorder (PTSD), generalized anxiety severity stress/coping skills, pain, and fatigue. Results: The RWC showed high participant engagement, with an 84%-95% attendance engagement rate depending on suicide risk history. Data from 15 cohorts (N = 126) demonstrate favorable outcomes associated with participation in this comprehensive program, as evidenced by a reduction in suicidal ideation, depression, and hopelessness, but not sleep quality and diet. In addition, in a subset of veterans with a history of suicidal ideation or attempt, significant improvements were noted in pain, PTSD/anxiety symptoms, and stress coping measures. Conclusions: The RWC shows that an intensive complement of CIH interventions is associated with a significant improvement with high veteran engagement. Findings from this program evaluation study can be used to aid health care systems and their providers in determining whether or not to utilize such multimodal CIH integrated interventions as an effective treatment for at-risk populations as a part of suicide prevention efforts.

Jatrorrhizine Hydrochloride Suppresses Proliferation, Migration, and Secretion of Synoviocytes In Vitro and Ameliorates Rat Models of Rheumatoid Arthritis In Vivo.

Jatrorrhizine hydrochloride (JH), an active component isolated from the traditional Chinese herb Coptis chinensis, has been reported to have antimicrobial, antitumor, antihypercholesterolemic, and neuroprotective activities. However, its antirheumatoid arthritis (RA) property remains unknown. In this study, a collagen-induced arthritis (CIA) rat model was used to evaluate the therapeutic effects of JH on RA by using arthritis score, radiological evaluation, and histopathological assessment. The in vitro effects of JH on proliferation, migration, and production of inflammatory mediators in RA-derived fibroblast-like synoviocyte MH7A cells were determined by the EdU incorporation assay, wound healing assay, real-time PCR, and ELISA, respectively. The in vivo studies showed that JH treatment significantly prevented the progression and development of RA in CIA rats through anti-inflammation and suppressing bone destruction. The in vitro studies revealed that JH could effectively attenuate the destructive phenotypes of MH7A cells, including inhibiting proliferation, migration, and production of inflammatory mediators. Further mechanistic analysis demonstrated that JH suppressed tumor necrosis factor alpha (TNFα)-stimulated activations of nuclear factor of kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) (ERK and p38) leading to the downregulation of proinflammatory cytokines, which might be beneficial to the antiproliferative and antimigratory activities of FLS cells. Collectively, our results demonstrated that JH has a great potential to be developed into a novel therapeutic agent for treating RA.

Resveratrol suppresses lipoprotein-associated phospholipase A2 expression by reducing oxidative stress in macrophages and animal models.

SCOPE: Resveratrol is a naturally occurring polyphenolic compound with known cardioprotective, anti-inflammatory, and antioxidant properties. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with the risk of cardiovascular disease. Here, we investigated the effects of resveratrol on Lp-PLA2 expression in vitro and in vivo and explored the underlying mechanisms. METHODS AND RESULTS: Human monocytic cells (THP-1) were induced to differentiate into macrophages for an in vitro experimental model. Resveratrol suppressed Lp-PLA2 expression and reduced inflammation; lipopolysaccharide (LPS, 1 µg/mL), tumor necrosis factor-α (TNF-α, 10 ng/mL) and reactive oxygen species (ROS) were employed to stimulate an increase in Lp-PLA2 expression and ROS levels, and the stimulation was inhibited by resveratrol (50 µM) and other antioxidants. The inhibition of resveratrol was inversed partially by sirtuin 1 (SIRT1) inhibitors (Nicotinamide, 1-10 mM) (p<0.05). Next, a chronic inflammation mouse model induced by a HFD (high fat diet) supplemented with resveratrol 100 mg/kg/day orally for 12 weeks, resulted in resveratrol-induced decreases in the Lp-PLA2 levels in the plasma and liver and increases in the superoxide dismutase 2 (SOD2) expression in the liver (p<0.05). CONCLUSION: Based on our results, the protective effects of resveratrol on cardiovascular events may be related to its ability to suppress Lp-PLA2 expression.

Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro.

Endothelin-1 (ET-1) autocrine and paracrine signaling modulate cell proliferation of tumor cells by activating its receptors, endothelin A receptor (ETAR) and endothelin B receptor (ETBR). Dysregulation of ETAR activation promotes tumor development and progression. The potential of ETAR antagonists and the dual-ETAR and ETBR antagonists as therapeutic approaches are under preclinical and clinical studies. Salvianolic acid A (Sal A) is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge (Danshen), which has been reported as an anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate that Sal A inhibits ETAR activation induced by ET-1 in both recombinant and endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively. Furthermore, our results showed that Sal A suppressed cell proliferation and extended the doubling times of multiple cancer cells, including HeLa, DU145, H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145 cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells (HUVEC) and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity. Collectively, our findings indicate that Sal A is a novel anti-cancer candidate through targeting ETAR.

Cycloastragenol, a triterpene aglycone derived from Radix astragali, suppresses the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.

Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 value of 13.0 µM. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 µM. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50 value was determined as 21.9 µM. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.

[6]-gingerol: a novel AT1 antagonist for the treatment of cardiovascular disease.

Considering the prevalence of cardiovascular disease in public health and the limited validated therapeutic options, this study aimed to find novel compounds targeting the angiotensin II type 1 receptor, accepted as a therapeutic target in cardiovascular disease. A small library consisting of 89 compounds from 39 Chinese herbs was profiled using a cell-based calcium mobilization assay which was developed and characterized for high-throughput screening. [6]-Gingerol derived from Zingiber officinale Roscoe (ginger) was identified as a novel angiotensin II type 1 receptor antagonist, with an IC50 value of 8.173 µM. The hit was further tested by a specificity assay indicating that it had no antagonistic effects on other evaluated GPCRs, such as endothelin receptors. The major ingredient of ginger, [6]-gingerol, could inhibit angiotensin II type 1 receptor activation, which partially clarified the mechanism of ginger regulating blood pressure and strengthening heart in the cardiovascular system.