Efficacy of endovascular embolization versus microsurgical clamping in the treatment of intracranial aneurysms: a meta-analysis.

Intracranial aneurysms (IA) can induce increased intracranial pressure, headache, and the development of nausea and vomiting if not treated in time, and failure to receive timely diagnosis and treatment can lead to disability or death. However, the efficacy and prognostic value of craniotomy and endovascular embolization in patients with IA remains a controversial topic. This meta-analysis systematically evaluated the efficacy of endovascular coiling versus cranial aneurysm clamping on the immediate postoperative outcome and prognosis of patients with IA. PubMed, EMBASE, and the Cochrane Library databases were searched for retrieval of relevant references. Literature was screened according to pre-defined inclusion and exclusion criteria, and data were extracted and assessed for quality. A total of 10 studies, including 2,654 cases, were included in the analysis. Among them, 1,313 cases underwent craniotomy clipping surgery (clip group), and 1,341 cases underwent endovascular coiling (coil group). The quality of the studies in 8 articles evaluated using the Newcastle-Ottawa Scale (NOS) was ≥6. Meta-analysis was conducted using Rev Man 5.3 and Stata 17 software. The results of meta-analysis showed that no significant difference in complete occlusion rate [OR=1.76, 95% CI (0.78, 3.96), P=0.17] when comparing the clip and coil group. Compared to the clip group, the coil group had a better clinical short-term outcome [OR=1.55, 95% CI (1.05, 2.27), P=0.03], but an increased rate of postoperative residual or recurrence [OR=0.40, 95% CI (0.17, 0.91), P=0.03]. In addition, there were no significance differences identified in terms of complications, including the rates of postoperative rebleeding [OR=1.60, 95% CI (0.97, 2.63), P=0.07], ischemic stroke [OR=1.12, 95% CI (0.45, 2.79), P=0.81], and cerebral vasospasm [OR=0.90, 95% CI (0.13, 6.03), P=0.91]. Subsequently, we conducted experimental sequence analysis for each indicator, and the results were consistent with the results of meta-analysis. According to the recent clinical prognosis, a funnel plot was constructed, showing significant asymmetry on both sides, indicating some publication bias. However, the results of Begg's test with P=0.734 and Egger's test with P=0.633 suggest no significant publication bias. In general, endovascular coiling and microsurgical clipping appear to be equally effective in achieving vascular occlusion. Endovascular coiling may be more effective in improving the short-term clinical outcomes for patients. However, this approach may increase the rate of postoperative residual issue or recurrence.

The effect of in vitro simulated colonic pH gradients on microbial activity and metabolite production using common prebiotics as substrates.

BACKGROUND: The interplay between gut microbiota (GM) and the metabolization of dietary components leading to the production of short-chain fatty acids (SCFAs) is affected by a range of factors including colonic pH and carbohydrate source. However, there is still only limited knowledge on how the GM activity and metabolite production in the gastrointestinal tract could be influenced by pH and the pH gradient increases along the colon. RESULTS: Here we investigate the effect of pH gradients corresponding to levels typically found in the colon on GM composition and metabolite production using substrates inulin, lactose, galactooligosaccharides (GOS), and fructooligosaccharide (FOS) in an in vitro colon setup. We investigated 3 different pH regimes (low, 5.2 increasing to 6.4; medium, 5.6 increasing to 6.8 and high, 6.0 increasing to 7.2) for each fecal inoculum and found that colonic pH gradients significantly influenced in vitro simulated GM structure, but the influence of fecal donor and substrate was more pronounced. Low pH regimes strongly influenced GM with the decreased relative abundance of Bacteroides spp. and increased Bifidobacterium spp. Higher in vitro simulated colonic pH promoted the production of SCFAs in a donor- and substrate-dependent manner. The butyrate producer Butyricimonas was enriched at higher pH conditions, where also butyrate production was increased for inulin. The relative abundance of Phascolarctobacterium, Bacteroides, and Rikenellaceae also increased at higher colonic pH, which was accompanied by increased production of propionate with GOS and FOS as substrates. CONCLUSIONS: Together, our results show that colonic substrates such as dietary fibres influence GM composition and metabolite production, not only by being selectively utilized by specific microbes, but also because of their SCFA production, which in turn also influences colonic pH and overall GM composition and activity. Our work provides details about the effect of the gradients of rising pH from the proximal to distal colon on fermenting dietary substrates in vitro and highlights the importance of considering pH in GM research.

Effect of Cyberlindnera jadinii yeast on growth performance, nutrient digestibility, and gut health of broiler chickens from 1 to 34 d of age.

The effect of dietary graded levels of Cyberlindnera jadinii yeast (C. jadinii) on growth performance, nutrient digestibility, and gut health of broilers was evaluated from 1 to 34 d of age. A total of 360 male broiler chicks were randomly allocated to 1 of 4 dietary treatments (6 replicate pens each) consisting of a wheat-soybean meal-based pelleted diet (Control or CJ0), and 3 diets in which 10% (CJ10), 20% (CJ20), and 30% (CJ30) of the crude protein were supplied by C. jadinii, by gradually replacing protein-rich ingredients. Body weight and feed intake were measured at d 1, 11, 22, and 32. Pellet temperature, durability, and hardness increased linearly (P < 0.05) with C. jadinii inclusion, with highest (P < 0.05) values for CJ30. Up until d 22, feed conversion ratio (FCR) was similar between treatments (P = 0.169). Overall, increasing C. jadinii inclusion linearly increased (P = 0.047) feed intake but had no effect on weight gain or mortality. FCR increased (P < 0.05) linearly with increasing C. jadinii inclusion but only birds fed CJ30 had a significantly poorer FCR compared to the Control. Ileal digestibility was not affected by C. jadinii inclusion, however, there was a significant linear decrease in crude protein and phosphorus, and a tendency for a decrease in fat digestibility. Apparent metabolizable energy (AME) decreased (P < 0.001) quadratically with increasing C. jadinii and was significantly lower in CJ30 compared to the Control. Ileal concentrations of volatile fatty acids (VFAs) were not affected by C. jadinii inclusion, but butyric acid and total VFAs were linearly and quadratically increased and were significantly higher in cecal digesta of birds fed CJ20 and CJ30. Increasing C. jadinii inclusion was associated with an increase (P < 0.05) in the relative abundance of lactobacillus in the ileum and cecum. In conclusion, C. jadinii yeast can supply up to 20% of the total dietary protein without negatively affecting performance, digestibility, or gut health of broilers. The potential confounding role of feed processing and C. jadinii cell wall components on broiler performance is discussed.

Comparison of percutaneous balloon compression and microvascular decompression in the treatment of trigeminal neuralgia.

Objective: To compare the effect of percutaneous balloon compression (PBC) and microvascular decompression (MVD) in the treatment of trigeminal neuralgia (TN). Methods: Data of 98 patients with TN, admitted to Chenzhou First People's Hospital from May 2020 to May 2022, were retrospectively collected. Patients were divided into two groups based on the surgical method. A total of 53 patients treated with PBC comprised the PBC-group and 45 patients treated with MVD comprised the MVD-group. The immediate pain relief, long-term efficacy, surgical complications, and masticatory muscle strength of the two groups were compared and analyzed. Results: There was no significant difference in the immediate pain relief and long-term e efficacy, between the two groups (P>0.05). Complication rate in the PBC-group was significantly lower than that in the MVD-group (3.77% vs 17.78%, P<0.05). Medical records within 14 days after the operation showed that the incidence of facial numbness and masticatory muscle weakness in the PBC-group were 37.74% and 28.30% respectively, significantly higher than those in MVD-group (4.44% and 2.22%) (P<0.05). These symptoms gradually improved three months after the surgery, and were almost completely resolved after six months. Conclusions: Compared with MVD, PBC has the same effect in the treatment of TN. PBC is a minimally invasive, safe, and effective method with a low complication rate. Although masticatory muscle strength is slightly impacted by PBC, it gradually recovers within six months after the operation.

Effect of truncation on TRPM7 channel activity.

Transient receptor potential melastatin-like 7 (TRPM7) is a key player in various physiological and pathological processes. TRPM7 channel activity is regulated by different factors. The effects of cleavage of different domains on channel activity remain unknown. Here, we constructed several TRPM7 clones and explored the effects of truncating the mouse TRPM7 at different locations on the ion channel activity in two cell lines. We compared the clones' activity with the full-length TRPM7 and the native TRPM7 in transfected and untransfected cells. We also expressed fluorescently tagged truncated clones to examine their protein stability and membrane targeting. We found that truncating the kinase domain induced reduction in TRPM7 channel activity. Further truncations beyond the kinase (serine/threonine rich domain and/or coiled-coil domain) did not result in further reductions in channel activity. Two truncated clones lacking the TRP domain or the melastatin homology domain had a completely nonfunctional channel apparently due to disruption of protein stability. We identified the shortest structure of TRPM7 with measurable channel activity. We found that the truncated TRPM7 containing only S5 and S6 domains retained some channel activity. Adding the TRP domain to the S5-S6 resulted in a significant increase in channel activity. Finally, our analysis showed that TRPM7 outward currents are more sensitive to truncations than inward currents. Our data provide insights on the effects of truncating TRPM7 at different locations on the channel functions, highlighting the importance of different domains in impacting channel activity, protein stability, and/or membrane targeting.

Soluble, Diferuloylated Corn Bran Glucuronoarabinoxylans Modulate the Human Gut Microbiota In Vitro.

Corn bran is exceptionally rich in substituted glucuronoarabinoxylan polysaccharides, which are monoferuloylated and cross-linked by diferulic acid moieties. Here, we assessed the potential prebiotic activity of three enzymatically solubilized corn bran glucuronoarabinoxylans: medium feruloylated (FGAX-M), laccase cross-linked FGAX-M (FGAX-H), and alkali-treated FGAX-M devoid of feruloyl substitutions (FGAX-B). We examined the influence of these soluble FGAX samples on the gut microbiome composition and functionality during in vitro simulated colon fermentations, determined by 16S rRNA gene amplicon sequencing and assessment of short-chain fatty acid (SCFAs) production. All FGAX samples induced changes in the relative composition of the microbiota and the SCFA levels after 24 h of in vitro fermentation. The changes induced by FGAX-M and FGAX-H tended to be more profound and more similar to the changes induced by inulin than changes conferred by FGAX-B. The microbiota changes induced by FGAX-M and FGAX-H correlated with an increase in the relative abundance of Anaerostipes and with increased butyric acid production, while the changes induced by the FGAX-B sample were less compelling. The results imply that solubilized, substituted diferuloylated corn bran glucuronoarabinoxylans may be potential prebiotic candidates and that both single feruloylations and diferuloyl cross-links influence the prebiotic potential of these arabinoxylan compounds.

Yogurt Benefits Bone Mineralization in Ovariectomized Rats with Concomitant Modulation of the Gut Microbiome.

SCOPE: Evidence supports that gut-modulating foods potentially can suppress bone loss in postmenopausal women. This study aims to investigate the effect of milk calcium-enriched milk, yogurt, and yogurt-inulin combination on the gut-bone association. METHODS AND RESULTS: A 6-week intervention study is conducted in ovariectomized rats. Four pastes containing milk calcium-fortified milk (M-Ca), milk calcium-fortified yogurt (Y-Ca), inulin-fortified Y-Ca (Y-I-Ca), or an isoconcentration of calcium carbonate (Ca-N), and a calcium-deficient paste are provided. M-Ca does not influence bone mineral density and content (BMD and BMC), femur mechanical strength, or femoral microstructure compared to Ca-N, but Y-Ca increases spine BMD. The serum metabolome reveals that Y-Ca modulated glycine-related pathways with reduced glycine, serine, and threonine. No additive effects of yogurt and inulin are found on bone parameters. Correlation analysis shows that increased lactobacilli and reduced Clostridiaceae members in Y-Ca is associated with an increased spine BMD. Increases in Bifidobacterium pseudolongum, Turicibacter, Blautia, and Allobaculum and gut short-chain fatty acids in Y-I-Ca are not reflected in bone parameters. CONCLUSION: Yogurt as calcium vehicle contributes to increased spine BMD concomitant with changes in the gut microbiome and glycine-related pathways, while adding inulin to yogurt does not affect bone mineralization in ovariectomized rats.

Effects of Calcium Source, Inulin, and Lactose on Gut-Bone Associations in an Ovarierectomized Rat Model.

SCOPE: Osteoporosis poses a health challenge especially for postmenopausal women. This study aims to explore nutritional strategies to counteract bone demineralization in ovarierectomized (OVX) rats. METHODS AND RESULTS: OVX rats (n = 49) are fed with one of six different diets, where two different calcium sources (dairy calcium or calcium carbonate) are provided alone or in combination with either inulin (5%) or lactose (0.5%). In addition, a calcium-deficient diet is included. Calcium supplementation increases intestinal concentrations of short-chain fatty acids (SCFAs) and the abundance of fecal Acinetobacter and Propionibacterium. Accompanied with these effects, rats fed with calcium-fortified diets have higher bone mineral density, bone mineral content and femur mechanical strength, lower serum levels of bone markers, and lower expression of calcium absorption-related genes (transient receptor potential vanilloid type 6 (TRPV6), calcium-binding protein (CaBP) compared with control. Inulin supplementation results in a markedly increased production of intestinal SCFAs, a decreased intestinal pH, an increased abundance of Allobaculum and Bifidobacterium, and an increased expression of Trpv6. Inulin and lactose show beneficial effects on spine bone. CONCLUSION: Calcium modulates gut microbiome composition and function. A pronounced effect of inulin on metabolic activity in the gastrointestinal tract is evident, and lactose supplementation decreases jejunal pH that might be associated with slightly enhanced bone mineralization.

In vitro fecal fermentation profiles and microbiota responses of pulse cell wall polysaccharides: enterotype effect.

The gut microbiota community of individuals is predominated by diverse fiber-utilizing bacteria, and might have distinct fermentation outcomes for a given dietary substrate. In this research, we isolated pea cell walls (PCWs) from cotyledon seeds, and performed the in vitro fecal fermentation by individual Prevotella- and Bacteroides-enterotype inocula. The Prevotella-enterotype inoculum showed a higher fermentation rate and produced more short-chain fatty acids (SCFAs), especially propionate and butyrate, throughout the entire fermentation period from PCW degradation compared with the Bacteroides-enterotype one. Furthermore, the better monosaccharide utilization capacity of Prevotella-enterotype inoculum was shown, compared to the Bacteroides-enterotype inoculum. PCW fermentation with Prevotella- and Bacteroides-enterotype inocula resulted in different microbial changes, and the abundance of Prevotella and Bacteroides was promoted, respectively. These results may contribute to predicting the responses of Prevotella and Bacteroides enterotypes to diets and offer useful information in personalized nutrition.

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.

In vitro colonic fermentation profiles and microbial responses of propionylated high-amylose maize starch by individual Bacteroides-dominated enterotype inocula.

The concept of "enterotype" has been proposed to differentiate the gut microbiota between individual humans, and different dominant bacteria utilize fiber substrates with different fermentation properties and microbial changes. In this study, we made propionylated high-amylose maize starch and investigated both in vitro fecal fermentation properties and microbial responses by individual Bacteroides-dominated enterotype inocula. Propionyl group substitution of HAMS did not significantly change gas production profiles, suggesting that the gas production during fermentation is independent of propionylation. The final concentration of released propionate significantly increased (10.26-12.60 mM) as a function of propionylation degree, suggesting that the introduced propionyl groups can increase the concentration of short-chain fatty acids (SCFA) during colonic fermentation. At the genus level, Bacteroides was obviously promoted for all donors with the final abundance in the range of 0.1-0.24, indicating that propionylated high-amylose maize starch changed the structure and abundance of microbiota compared to unmodified starch. Besides, the non-metric dimensional scoring (NMDS) plots showed that those changes were related to the initial microbiota composition. The results may offer useful information for the design of personalized food products and relevant therapies at least within Bacteroides-dominated enterotype.

Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels.

Geissoschizine methyl ether (GM) is an indole alkaloid isolated from Uncaria rhynchophyll (UR) that has been used for the treatment of epilepsy in traditional Chinese medicine. An early study in a glutamate-induced mouse seizure model demonstrated that GM was one of the active ingredients of UR. In this study, electrophysiological technique was used to explore the mechanism underlying the antiepileptic activity of GM. We first showed that GM (1-30 µmol/L) dose-dependently suppressed the spontaneous firing and prolonged the action potential duration in cultured mouse and rat hippocampal neurons. Given the pivotal roles of ion channels in regulating neuronal excitability, we then examined the effects of GM on both voltage-gated and ligand-gated channels in rat hippocampal neurons. We found that GM is an inhibitor of multiple neuronal channels: GM potently inhibited the voltage-gated sodium (NaV), calcium (CaV), and delayed rectifier potassium (IK) currents, and the ligand-gated nicotinic acetylcholine (nACh) currents with IC50 values in the range of 1.3-13.3 µmol/L. In contrast, GM had little effect on the voltage-gated transient outward potassium currents (IA) and four types of ligand-gated channels (γ-amino butyric acid (GABA), N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainite (AMPA/KA receptors)). The in vivo antiepileptic activity of GM was validated in two electricity-induced seizure models. In the maximal electroshock (MES)-induced mouse seizure model, oral administration of GM (50-100 mg/kg) dose-dependently suppressed generalized tonic-clonic seizures. In 6-Hz-induced mouse seizure model, oral administration of GM (100 mg/kg) reduced treatment-resistant seizures. Thus, we conclude that GM is a promising antiepileptic candidate that inhibits multiple neuronal channels.

In vitro fecal fermentation of propionylated high-amylose maize starch and its impact on gut microbiota.

Resistant starch (RS) acylated with propionate groups is of particular interest in terms of their capacity to deliver specific short-chain fatty acids (SCFAs) to the colon with health benefits. In the present study, we fabricated propionylated high-amylose maize starches with different degrees of substitution (DS), and monitored the in vitro human fecal fermentation profiles. Propionylated modification did not change the slow gas production properties of high-amylose maize starch throughout the whole fermentation period. The final concentration of propionate (13.68-21.10 mM) produced by propionylated starch fermentation enhanced gradually with increase of DS value, resulting from the release of introduced propionyl groups. Certain beneficial gut microbiota such as Roseburia, and Blautia were obviously promoted, suggesting that propionylated starch could regulate the composition of gut microbiota. The results may facilitate the design and manufacture of functional food products with the aim of improving colonic health.

ß-carotene provides neuro protection after experimental traumatic brain injury via the Nrf2-ARE pathway.

We investigate whether ß-carotene, a known natural antioxidant, can reduce oxidative stress induced by traumatic brain injury. In addition, we investigated the underlying mechanism of traumatic brain injury focusing on the NF-E2-related factor (Nrf2) pathway. A controlled cortical impact model was used to mimic traumatic brain injury. Using this model, we evaluated brain edema, lesion volume, neurologic deficits, reactive oxygen species, and the expression of Nrf2-related protein markers. The results of our study demonstrated that cognitive performance and neural functions were improved with ß-carotene administration. In addition, ß-carotene reduced brain edema and reactive oxygen species levels after traumatic brain injury. Nrf2 nuclear accumulation was increased and was accompanied by decreased Keap1 expression. The expression of quinone oxidoreductase 1, a target gene of the Nrf2 signaling pathway was increased. However, lesion volume was not significantly reduced after ß-carotene treatment. Taken together, our data demonstrated that ß-carotene administration was neuroprotective and alleviated oxidative stress by modulating the Nrf2/Keap1- mediated antioxidant pathway in the traumatic brain injury model.