The impact of sarcopenia on the incidence of postoperative outcomes following spine surgery: Systematic review and meta-analysis.

PURPOSE: Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015). CONCLUSION: The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.

Serine synthesis controls mitochondrial biogenesis in macrophages.

Mitochondrial dysfunction is the pivotal driving factor of multiple inflammatory diseases, and targeting mitochondrial biogenesis represents an efficacious approach to ameliorate such dysfunction in inflammatory diseases. Here, we demonstrated that phosphoglycerate dehydrogenase (PHGDH) deficiency promotes mitochondrial biogenesis in inflammatory macrophages. Mechanistically, PHGDH deficiency boosts mitochondrial reactive oxygen species (mtROS) by suppressing cytoplasmic glutathione synthesis. mtROS provokes hypoxia-inducible factor-1α signaling to direct nuclear specificity protein 1 and nuclear respiratory factor 1 transcription. Moreover, myeloid Phgdh deficiency reverses diet-induced obesity. Collectively, this study reveals that a mechanism involving de novo serine synthesis orchestrates mitochondrial biogenesis via mitochondrial-to-nuclear communication, and provides a potential therapeutic target for tackling inflammatory diseases and mitochondria-mediated diseases.

Targeting methionine metabolism in cancer: opportunities and challenges.

Reprogramming of methionine metabolism is a conserved hallmark of tumorigenesis. Recent studies have revealed mechanisms regulating methionine metabolism within the tumor microenvironment (TME) that drive both cancer development and antitumor immunity evasion. In this review article we summarize advancements in our understanding of tumor regulation of methionine metabolism and therapies in development that target tumor methionine metabolism. We also delineate the challenges of methionine blockade therapies in cancer and discuss emerging strategies to address them.

Serine synthesis sustains macrophage IL-1ß production via NAD+-dependent protein acetylation.

Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1ß production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1ß expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1ß maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1ß production, providing a potential inflammatory disease target.

Influence of Experimental Skull Defects on Brain.

ABSTRACT: This study was aimed to observe the effects of skull defects on the brain in rats and further to investigate its underlying pathophysiological. Three different sizes of skull were removed in rats to produce models of skull defect, and then the behavioral changes were detected using a grip strength meter and neurobehavioral severity scale scores. The authors further examined the levels of cell apoptosis and autophagy, the cerebral blood flow with immunoblotting, and immunofluorescence micro-ultrasound system, respectively. The authors found that the sensory function but not the grip was impaired on the 6th day after a 5 × 10 mm defect while the motor function was on the 2nd day. In addition, the authors found an increment in B-cell lymphoma-2/BCL2-Associated X (Bcl2/Bax) and LC3 II/I expression, a maker of apoptosis and autophagy, respectively, in the defective hemisphere especially at the edge of the defective area. Importantly, the blood flow of internal carotid artery began to decline at 2 hours, and reached minimum on the 4th day, but began to recover on the 6th day in the hemi-defect group. In conclusion, a larger skull defect could impair the cognitive function but not the motor function and its underlying pathophysiology were mainly related to a decrease in cerebral flow.

Minimally invasive surgery for hilar cholangiocarcinoma: a multicenter retrospective analysis of 158 patients.

BACKGROUND: Curative resection of hilar cholangiocarcinoma (HC) is typically carried out using open surgery. In the present study, we examined the safety (postoperative complication) and effectiveness (resection margin status and patient survival) of minimally invasive surgery (MIS) for HC. METHODS: This retrospective analysis included 158 patients receiving MIS for HC at 10 participating centers between December 2013 and November 2019. Patient demographics, surgical outcomes, and oncological outcomes were retrospectively analyzed. RESULTS: Clinical information obtained from 10 different clinical centers did not show any evident cohort-bias clustering. One hundred and twenty-six (79.7%) patients underwent LRHC, 12 (7.6%) patients underwent RARHC, conversion to an open procedure occurred in 20 (12.7%) patients. The operation time and estimated blood loss were 410.8 ± 128.9 min and 477.8 ± 706.3 mL, respectively. The surgical radicality of the 158 patients was R0, 129 (81.6%); R1, 20 (18.4%) and R2, 9 (5.7%). Grades I-II complications was occurred in 68 (43.0%) patients. Severe morbidity (grade III-V) occurred in 14 (8.7%) patients. The median overall survival in whole cohort was 25.4 months. The overall survival rate was 67.6% at year 1, 28.8% at year 3, and 19.2% at year 5. Comparing the first half of MISHC performed by each center with the following cases, the operation time and postoperative hospital stay does not decrease with the increasing cases. On literature review, MISHC is non-inferior to open surgery at least in perioperative period. CONCLUSIONS: In this Chinese MIS for HC multicenter study, the largest to date, long-term overall survival rates after MIS appear comparable to those reported in current open series. Further randomized controlled trials are necessary to assess the global impact of MISHC.

Perspective: Methionine Restriction-Induced Longevity-A Possible Role for Inhibiting the Synthesis of Bacterial Quorum Sensing Molecules.

Methionine restriction (MR) extends lifespans in multiple species through mechanisms that include enhanced oxidative stress resistance and inhibition of insulin/insulin-like growth factor I (IGF-I) signaling. Methionine and S-adenosylmethionine (SAM) are the essential precursors of bacterial quorum sensing (QS) molecules, and therefore, MR might also affect bacterial communication to prevent enteric bacterial infection as well as chronic inflammation, which contributes to lifespan prolongation. Here, we discuss the influence of MR on oxidative stress resistance and inhibition of insulin/IGF-I cell signaling and further propose a potential mechanism involving bacterial QS inhibition for lifespan extension. Unraveling the connection between MR and inhibition of QS provides new strategies for combating infectious diseases, resulting in enriched understanding of MR-induced lifespan extension.

Sulfur-containing amino acid supplementation to gilts from late pregnancy to lactation altered offspring's intestinal microbiota and plasma metabolites.

Maternal nutrition during late pregnancy and lactation is highly involved with the offspring's health status. The study was carried out to evaluate the effects of different ratios of methionine and cysteine (Met/Cys: 46% Met, 51% Met, 56% Met, and 62% Met; maintained with 0.78% of total sulfur-containing amino acids; details in "Materials and methods") supplements in the sows' diet from late pregnancy to lactation on offspring's plasma metabolomics and intestinal microbiota. The results revealed that the level of serum albumin, calcium, iron, and magnesium was increased in the 51% Met group compared with the 46% Met, 56% Met, and 62% Met groups. Plasma metabolomics results indicated that the higher ratios of methionine and cysteine (0.51% Met, 0.56% Met, and 0.62% Met)-supplemented groups enriched the level of hippuric acid, retinoic acid, riboflavin, and δ-tocopherol than in the 46% Met group. Furthermore, the 51% Met-supplemented group had a higher relative abundance of Firmicutes compared with the other three groups (P < 0.05), while the 62% Met-supplemented group increased the abundance of Proteobacteria compared with the other three groups (P < 0.05) in piglets' intestine. These results indicated that a diet consisting with 51% Met is the optimum Met/Cys ratio from late pregnancy to lactation can maintain the offspring's health by improving the serum biochemical indicators and altering the plasma metabolomics profile and intestinal gut microbiota composition, but higher proportion of Met/Cys may increase the possible risk to offspring's health.

Negative effects on newborn piglets caused by excess dietary tryptophan in the morning in sows.

BACKGROUND: This study investigated the effect of dynamic feeding models of dietary tryptophan on sows' performance during late pregnancy. RESULTS: The average piglet birth weight and live farrowing rate from sows consuming a high-low tryptophan diet (0.39% Trp in the morning and 0.13% Trp in the afternoon) were decreased compared with those fed a 2×tryptophan diet (0.26% Trp in the morning and afternoon). Compared with the 2×tryptophan group, sow serum kynurenic acid and the newborn liver n-6:n-3 polyunsaturated fatty acid ratio were significantly higher, and sow serum taurine and newborn serum taurine, phosphoserine, cysteine and proline were lower in the high-low tryptophan diet group. Eighty-eight genes were differentially expressed in newborn piglets' livers between the 2×tryptophan and high-low groups. Genes related to cytotoxic effector regulation (major histocompatibility complex class I proteins), NADH oxidation, reactive oxygen species (ROS) metabolism and tissue development were differentially expressed between these two groups. CONCLUSION: Together, the results provide information on new biomarkers in serum or liver and provide novel insights into variations in the fetal liver during exogenous stimulus response and biological processes of ROS metabolism in fetuses during late pregnancy caused by a single excessive tryptophan ingestion daily in the morning. © 2018 Society of Chemical Industry.

The role of methionine on metabolism, oxidative stress, and diseases.

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases.

DNA Methylation and the Potential Role of Methyl-Containing Nutrients in Cardiovascular Diseases.

Patients suffering from cardiovascular diseases (CVDs) experience a low quality of life and increase pressure on healthcare systems both nationally and globally. DNA methylation, which refers to the pathway by which DNA methyltransferase facilitates the addition of a methyl group to DNA, is of critical importance in this respect primarily because the epigenetic modification is implicated in a range of serious conditions including atherosclerosis, CVDs, and cancer. Research findings indicate that the number of epigenetic alterations can be elicited (both in utero and in adults) through the administration of certain nutritional supplements, including folic acid and methionine; this is partly attributable to the effect employed by methyl-containing nutrients in DNA methylation. Thus, for the purpose of illuminating viable therapeutic measures and preventive strategies for CVDs, research should continue to explore the intricate associations that exist between epigenetic regulation and CVD pathogenesis. This review centers on an exposition of the mechanism by which DNA methylation takes place, the impact it has on a range of conditions, and the potential clinical value of nutrition, driven mainly by the observation that nutritional supplements such as folic acid can affect DNA methylation.

Oxidation Resistance of the Sulfur Amino Acids: Methionine and Cysteine.

Sulfur amino acids are a kind of amino acids which contain sulfhydryl, and they play a crucial role in protein structure, metabolism, immunity, and oxidation. Our review demonstrates the oxidation resistance effect of methionine and cysteine, two of the most representative sulfur amino acids, and their metabolites. Methionine and cysteine are extremely sensitive to almost all forms of reactive oxygen species, which makes them antioxidative. Moreover, methionine and cysteine are precursors of S-adenosylmethionine, hydrogen sulfide, taurine, and glutathione. These products are reported to alleviate oxidant stress induced by various oxidants and protect the tissue from the damage. However, the deficiency and excess of methionine and cysteine in diet affect the normal growth of animals; thereby a new study about defining adequate levels of methionine and cysteine intake is important.

[Clinical analysis of relapsing anti-N-methyl-D-aspartate receptor encephalitis].

OBJECTIVE: With the discovery of more patients with anti-N-methyl-D-aspartate (anti- NMDAR) encephalitis, frequent clinical relapses pose a new challenge to neurologists. METHODS: Retrospective reviews were conducted for 16 hospitalized patients with relapsing anti-NMDAR encephalitis at our hospital from June 2011 until November 2014. Their clinical data including symptoms, cerebrospinal fluid (CSF) profiles, neuroimaging findings and relapsing treatment were compared with those initial episodes. RESULTS: There were 11 females and 5 males with a mean onset time of 21.2 (10-34) years. For initial episodes, the mean number of major symptoms was 5. 8 and the mean modified Rankin score (mRS) 4.56. And 7 (43.8%) cases were admitted into intensive care unit (ICU). All received first-line immunotherapy and only one case second-line immunotherapy. Ovarian teratoma was detected and resected in only one case of initial episode. Among 32 relapses, 8 cases (50% ) had multiple (2-4) relapses. There was a median delay of 5.0 (0.5-18) months for relapses. Relapses were common upon pausing or reducing immunotherapy, usually monotherapy with corticosteroids. Compared with initial episodes, relapses were less severe (mean mRS 2.69, mean number of symptom 2.59) and only 2 cases were admitted into ICU during relapses. Presentation of relapses were partial symptoms of initial episode. However, two patients had new symptoms of brain stem involvement. Brain magnetic resonance imaging (MRI) of 8 cases showed abnormality initially during initial episode and disappearance at relapses while new lesions appeared in 7 patients including 3 cases with CNS demyelinating features of central nervous system ( CNS) on MRI. The positivity rate of anti-NMDAR antibody was 100% in CSF and 53.1% in sera during relapses. Anti-AQP4 and NMO-Ig were positive in one case with brain stem involvement. All cases received first-line immunotherapy and 12 chronic second-line immunotherapy. Two cases of ovarian teratoma were detected on reassessment during relapse and then resected. CONCLUSION: Inadequacy of second-line and chronic immunotherapy, occult teratoma and potential demyelination may contribute to a relapse of anti-NMDAR encephalitis. And its proper management should follow the recommendations of guidelines.