Can the combination of antiplatelet or alteplase thrombolytic therapy with argatroban benefit patients suffering from acute stroke? a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is presently uncertain. However, it is important to highlight the potential benefits of combining this medication with known thrombolytics or antiplatelet therapy. One notable advantage of argatroban is its short half-life, which helps minimize excessive anticoagulation and risk of bleeding complications in inadvertent cases of hemorrhagic stroke. By conducting a meticulous review and meta-analysis, we aim to further explore the common use of argatroban and examine the plausible advantages of combining this medication with established thrombolytic and antiplatelet therapies. METHOD: In this study, we performed a rigorous and methodical search for both randomized controlled trials and retrospective analyses. Our main objective was to analyze the impact of argatroban on the occurrence of hemorrhagic events and the mRS scores of 0-2. We utilized a meta-analysis to assess the relative risk (RR) associated with using argatroban versus not using it. RESULTS: In this study, we analyzed data from 11 different studies, encompassing a total of 8,635 patients. Out of these patients, 3999(46.3%) received argatroban treatment while the remaining 4636(53.7%)did not. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score≤2) showed that the risk ratio (RR) for patients using argatroban after alteplase thrombolytic therapy compared to those not using argatroban was(RR, 1.00 ([95% CI, 0.92-1.09]; P = 0.97), indicating no statistical significance. However, for patients using argatroban after antiplatelet therapy, was (RR,1.09 [95% CI, 1.04-1.14]; P = 0.0001), which was statistically significant. In terms of hemorrhagic events, the RR for patients using argatroban compared to those not using argatroban was (RR,1.08 [95% CI, 0.88-1.33]; P = 0.46), indicating no statistical significance. CONCLUSION: The results of this study suggest that further research into combination therapy with argatroban and antiplatelet agents may be warranted, however more rigorous RCTs are needed to definitively evaluate the effects of combination treatment.

Interaction mechanism between luteoloside and corn silk glycans and the synergistic role in hypoglycemic activity.

As the two most principal active substances in the corn silk, polysaccharides and flavonoids, the mechanism of interaction between them has been a topic of intense research. This study provides an in-depth investigation of the interaction mechanism between corn silk glycans and luteoloside (LUT) and the synergistic role that result from this interaction. The interaction mechanism was evaluated by isothermal titration calorimetry (ITC) and circular dichroism (CD), and the synergistic role was evaluated by the expression of glucose transporters (GLUT-1), insulin secretion and surface plasmon resonance (SPR). CD and ITC results indicated that the interaction between CSGs and LUT mainly driven by the Cotton effects, enthalpy and entropy-driven. This interaction precipitated the formation of complexes (CSGs/LUT complexes) between corn silk glycans (CSGs) with four different molecular weights and luteoloside (LUT). Furthermore, the CSGs and LUT play a synergistic role in glucose regulation through GLUT-1 expression and insulin secretion experiments, compared to single luteoloside group.

Does Endovascular Thrombectomy(ET) plus tirofiban benefit stroke patients: A systematic review and meta-analysis.

BACKGROUND: Ischemic stroke is the second leading cause of death worldwide. Endovascular thrombectomy (ET) has been shown to prevent disability in a proportion of patients. The use of tirofiban in patients undergoing ET after acute stroke has resulted in improved patient function and reduced mortality to some extent. In this systematic review and meta-analysis of the current period, an overview of the most recent studies on the potential efficacy of using tirofiban to help acute stroke patients improve function and reduce mortality was provided. METHODS: In this meta-analysis, we explore the safety and efficacy of ET combined with tirofiban in patients with acute stroke. We searched the PubMed, EMBASE, Web of Science, and The Cochrane Library database from the construction of the library to the present relevant RCTs/non-RCTs. The following key words were used for finding relevant studies from the databases"tirofiban""thrombectomy"" Stroke"" balloon angioplasty""stenting". RESULTS: Total of 14 trials with 4366 individuals enrolled were included in the Meta-analysis including 2732(62.6) who received ET alone and 1634(37.4 %) who received tirofiban plus ET. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score≤2) was 42.2 % (1043/2473) in the ET alone group vs. 46.2 % (684/1480) in the tirofiban with ET group (risk ratio (RR), 1.10 [95 % CI, 1.02-1.18]; P=0.02),mortality at 90 days (RR, 0.86 [95 % CI, 0.76-0.98]; P = 0.02). There is no significant between-group differences were found in excellent outcome (mRS score ≤1) (RR, 1.08 [95 % CI, 0.95-1.23]; P = 0.22), symptomatic intracranial hemorrhage (RR, 1.11 [95 % CI, 0.92-1.34]; P = 0.27). CONCLUSIONS: These findings suggest that the use of ET combined with tirofiban in patients with acute stroke is safe and has the potential to reduce mortality and improve functional independence at 90 days.

Both natural and anthropogenic factors control surface water and groundwater chemistry and quality in the Ningtiaota coalfield of Ordos Basin, Northwestern China.

An understanding of the vertical variations in hydrogeochemical processes in various aquifers and quality suitability assessment is crucial for the utilization of groundwater in the Ningtiaota coalfield of Ordos Basin, Northwestern China. Based on 39 water samples collected from surface water (SW), Quaternary pore water (QW), weathered fissure water (WW), and mine water (MW), we conducted self-organizing maps (SOM) algorithm, multivariate statistical analysis (MSA), and classical graphical methods to elucidate the mechanisms controlling the vertical spatial variations in SW and groundwater chemistry and conducted a health risk assessment. The findings indicated that the hydrogeochemical type showed a transition from the HCO3--Na+ type in SW to the HCO3--Ca2+ type in QW, then to the SO42--Mg2+ type in WW, and back to HCO3--Na+ type in MW. Water-rock interaction, silicate dissolution, and cation exchange were the main hydrogeochemical processes in the study area. Additionally, groundwater residence time and mining operations were critical external factors that affect water chemistry. Contrary to phreatic aquifers, confined aquifers featured greater circulation depth, water-rock interactions, and external interventions leading to worse quality and higher health risks. Water quality surrounding the coalfield was poor, causing it to be undrinkable, with excessive SO42-, arsenic (As), and F-, etc. Approximately 61.54% of SW, all of QW, 75% of WW, and 35.71% of MW can be used for irrigation.

Modulation of CXCR1 and CXCR3 expression on NK cells via Tim-3 in a murine model of primary biliary cholangitis.

Tim-3, which is expressed on a variety of innate immune cells including NK cells, plays a key role in many autoimmune diseases. However, the immunomodulatory actions of Tim-3 on NK cells in primary biliary cholangitis (PBC) remain uncertain. Using a murine model of PBC we evaluated the expression of Tim-3 and its ligand Gal-9 in peripheral blood, liver, and spleen. Additionally, we studied Tim-3 regulation of chemokine receptors (CXCR1 and CXCR3) in vitro. Flow cytometric analysis indicated large numbers of infiltrating NK cells in the liver which exhibited high expression of Tim-3 and CXCR3. Moreover, we found overexpression of CXCR1 in liver tissue and liver-derived NK cells in PBC mice. We also observed lower levels of soluble Tim-3 in the serum of PBC mice. In vitro experiments with liver-derived NK cells from PBC mice indicated that CXCR3 was up-regulated by treatment with recombinant mouse TIM-3 Fc (rmTim-3 Fc) to activate the Tim-3 pathway. Furthermore, stimulating normal mouse spleen NK cells with poly I:C resulted in elevated expression of CXCR1 and interferon-γ release. Nonetheless, adding rmTim-3 Fc or rmGal-9 significantly down-regulated CXCR1 expression and IFN-γ release in NK cells activated by poly I:C, proposing a means to exploit the Tim-3 pathway to reverse responses in NK cells. In conclusion, our data demonstrate that dysregulation of Tim-3/Gal-9 is involved in modulating the local immune microenvironment in PBC mice. Our findings highlight the potential of Tim-3 pathway to modulate chemokine responses in NK cells during autoimmunity.

Tauroursodeoxycholic acid attenuates neuronal apoptosis via the TGR5/ SIRT3 pathway after subarachnoid hemorrhage in rats.

BACKGROUND: Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH. METHODS: Sprague-Dawley rats were subjected to model of SAH and TUDCA was administered via the internal carotid injection. Small interfering RNA (siRNA) for TGR5 were administered through intracerebroventricular injection 48 h before SAH. Neurological scores, brain water content, Western blot, TUNEL staining and immunofluorescence staining were evaluated. RESULTS: TUDCA alleviated brain water content and improved neurological scores at 24 h and 72 h after SAH. TUDCA administration prevented the reduction of SIRT3 and BCL-2 expressions, as well as the increase of BAX and cleaved caspase-3.Endogenous TGR5 expression were upregulated after SAH and treatment with TGR5 siRNA exacerbated neurological outcomes after SAH and the protective effects of TUDCA at 24 h after SAH were also abolished by TGR5 siRNA. CONCLUSIONS: Our findings demonstrate that TUDCA could attenuated neuronal apoptosis and improve neurological functions through TGR5/ SIRT3 signaling pathway after SAH. TUDCA may be an attractive candidate for anti-apoptosis treatment in SAH.

Bone marrow mesenchymal stem cells differentiate into intestinal epithelioid cells through the ERK1/2 pathway.

BACKGROUND/AIMS: Previous studies have found that the injection of rat bone marrow mesenchymal stem cells (rBMSCs) in a mouse model of acute hepatic failure significantly relieves intestinal damage and endotoxemia. However, the mechanism of this process remains unknown. This study demonstrated the differentiation of rBMSCs into enterocyte-like cells and possible molecular mechanisms for this with the aim of finding a new treatment for intestinal epithelial injury and endotoxemia during liver failure. MATERIALS AND METHODS: rBMSCs were isolated from rat femurs and tibias. Differentiation was induced by co-culturing rBMSCs with rat intestinal epithelial cells (mIEC-6) using Transwell plates; after three, seven, and ten days of induction, expression of specific differentiation molecules were quantified. To inhibit the activity of the Mitogen-activated protein kinase 1/2 (ERK1/2) signaling pathway, an inhibitor of Mitogen-activated protein kinase kinase 1/2 (MEK1/2) was added to the co-culture medium, and western blot analysis was performed after 36 or 72 h to evaluate the expression of ERK1/2 signaling pathway markers (p-MEK1/2 and p-ERK1/2). RESULTS: The rBMSCs differentiated into enterocyte-like cells when co-cultured with mIEC-6 cells. Inhibition of ERK1/2 signaling abrogated the activity of MEK1/2, but MEK increased after 72 h, and the epithelioid differentiation of rBMSCs was consistent with the change in MEK expression. CONCLUSION: rBMSCs differentiate into intestinal epithelium after co-culture with mIEC-6 by regulation of the ERK1/2 signaling pathway. Further research is needed to elucidate the network of mechanisms.

Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

Tauroursodeoxycholic acid attenuates neuronal apoptosis via the TGR5/ SIRT3 pathway after subarachnoid hemorrhage in rats

BACKGROUND: Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH. METHODS: Sprague-Dawley rats were subjected to model of SAH and TUDCA was administered via the internal carotid injection. Small interfering RNA (siRNA) for TGR5 were administered through intracerebroventricular injection 48 h before SAH. Neurological scores, brain water content, Western blot, TUNEL staining and immunofluorescence staining were evaluated. RESULTS: TUDCA alleviated brain water content and improved neurological scores at 24 h and 72 h after SAH. TUDCA administration prevented the reduction of SIRT3 and BCL-2 expressions, as well as the increase of BAX and cleaved caspase-3.Endogenous TGR5 expression were upregulated after SAH and treatment with TGR5 siRNA exacerbated neurological outcomes after SAH and the protective effects of TUDCA at 24 h after SAH were also abolished by TGR5 siRNA. CONCLUSIONS: Our findings demonstrate that TUDCA could attenuated neuronal apoptosis and improve neurological functions through TGR5/ SIRT3 signaling pathway after SAH. TUDCA may be an attractive candidate for anti-apoptosis treatment in SAH.

Extranodal natural killer/T-cell lymphoma nasal type with central nervous system involvement mimicked tuberculous meningitis: A case report.

RATIONALE: Neurologic deficits are rare in patients with extranodal natural killer/T-cell lymphoma (NKTL), nasal type. We present a case that was initially suspected as tuberculous meningitis, but later diagnosed as central nervous system metastasis of NKTL, nasal type, which has never been published previously. PATIENT CONCERNS: A 55-year-old Chinese man presented with persistent headache and fever. The initial head computed tomography and magnetic resonance imaging (MRI) scan was normal. Low glucose, elevated protein, and pleocytosis of cerebral spinal fluid led to a diagnosis of tuberculous meningitis. The patient did not respond to anti-tuberculosis treatment, and his symptoms aggravated. MRI showed abnormal lesions in the right hemisphere and a lesion in the maxillary sinus region. DIAGNOSIS: Endoscopic biopsy of the maxillary lesion showed features consistent with NKTL. Positron emission tomography revealed a hypermetabolic mass involving the right maxillary sinus and brain. INTERVENTIONS: The patient received chemotherapy. OUTCOMES: The patient died 30 days after chemotherapy. LESSONS: Lymphoma of the nasal cavity and paranasal sinuses is extremely rare and may be easily misdiagnosed. Nasal NKTL metastasis should be considered when a patient presents with symptoms of leptomeningeal involvement.

Response of bacterioplankton communities to cadmium exposure in coastal water microcosms with high temporal variability.

Multiple anthropogenic disturbances to bacterial diversity have been investigated in coastal ecosystems, in which temporal variability in the bacterioplankton community has been considered a ubiquitous process. However, far less is known about the temporal dynamics of a bacterioplankton community responding to pollution disturbances such as toxic metals. We used coastal water microcosms perturbed with 0, 10, 100, and 1,000 µg liter(-1) of cadmium (Cd) for 2 weeks to investigate temporal variability, Cd-induced patterns, and their interaction in the coastal bacterioplankton community and to reveal whether the bacterial community structure would reflect the Cd gradient in a temporally varying system. Our results showed that the bacterioplankton community structure shifted along the Cd gradient consistently after a 4-day incubation, although it exhibited some resistance to Cd at low concentration (10 µg liter(-1)). A process akin to an arms race between temporal variability and Cd exposure was observed, and the temporal variability overwhelmed Cd-induced patterns in the bacterial community. The temporal succession of the bacterial community was correlated with pH, dissolved oxygen, NO3 (-)-N, NO2 (-)-N, PO4 (3-)-P, dissolved organic carbon, and chlorophyll a, and each of these parameters contributed more to community variance than Cd did. However, elevated Cd levels did decrease the temporal turnover rate of community. Furthermore, key taxa, affiliated to the families Flavobacteriaceae, Rhodobacteraceae, Erythrobacteraceae, Piscirickettsiaceae, and Alteromonadaceae, showed a high frequency of being associated with Cd levels during 2 weeks. This study provides direct evidence that specific Cd-induced patterns in bacterioplankton communities exist in highly varying manipulated coastal systems. Future investigations on an ecosystem scale across longer temporal scales are needed to validate the observed pattern.