Preclinical safety and efficacy evaluation of the intrathecal transplantation of GMP-grade human umbilical cord mesenchymal stem cells for ischemic stroke.

Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke, but its safety, effectiveness, and mechanism remain to be elucidated. In this study, good manufacturing practice-grade human umbilical cord mesenchymal stem cells (5 × 105 and 1 × 106 cells) and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats. The results showed (1) no significant difference in mortality or general conditions among the three groups.

Temporal patterns and distribution of pyroptosis-related molecules and effects of human mesenchymal stem cells on pyroptosis following cerebral ischemia/reperfusion in rats.

Objectives: Pyroptosis is a new type of programmed cell death that has a strong proinflammatory effect. The present study investigated the dynamic changes of pyroptosis-related molecules and the effect of mesenchymal stem cells (MSCs) on pyroptosis following cerebral ischemia/reperfusion (I/R).

Materials And Methods: The temporal pattern and cellular distribution of caspase-1, Gasdermin D and E (GSDMD and GSDME) in the peri-infarct area, and the effect of human MSCs on GSDMD, IL-1β, IL-18, Lactate dehydrogenase (LDH) and neurological function were studied in a rat model of transient focal cerebral ischemia.

Post-thrombolysis early neurological deterioration occurs with or without hemorrhagic transformation in acute cerebral infarction: risk factors, prediction model and prognosis.

Objectives: Early neurological deterioration (END) after ischemic stroke is a severe clinical event and can be caused by hemorrhagic and ischemic injury. We studied the difference between the risk factors of END occurs with or without hemorrhagic transformation after intravenous thrombolysis.

Materials And Methods: Consecutive cerebral infarction patients who underwent intravenous thrombolysis from 2017 to 2020 in our hospital were retrospectively recruited.

Microglial and Neuronal Cell Pyroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation Aggravates Cell Injury via Activation of the Caspase-1/GSDMD Signaling Pathway.

Pyroptosis is a new type of programmed cell death, which induces a strong pro-inflammatory reaction. However, the mechanism of pyroptosis after brain ischemia/reperfusion (I/R) and the interaction between different neural cell types are still unclear. This study comprehensively explored the mechanisms and interactions of microglial and neuronal pyroptosisin the simulated I/R environment in vitro.

Enzymatic acylation of lutein with a series of saturated fatty acid vinyl esters and the thermal stability and anti-lipid oxidation properties of the acylated derivatives.

Lutein was enzymatically acylated with saturated fatty acid vinyl esters of different lengths of carbon chain (C -C ) under the action of Candida antarctica lipase B (Novozyme 435). The acylation reaction was optimized by considering substrate molar ratio, reaction solvent, type of enzyme, and reaction time. The highest yield (88%) was obtained using the Novozyme 435 to catalyze the acylation reaction of lutein and vinyl decanoate (lutein/vinyl decanoate molar ratio of 1/10) for 16 h in methyl tert-butyl ether.

Enzymatic acylation of rutin with benzoic acid ester and lipophilic, antiradical, and antiproliferative properties of the acylated derivatives.

Rutin (3',4',5,7-tetrahydroxy-flavone-3-rutinoside) was enzymatically acylated with benzoic acid and its esters (methyl benzoate and vinyl benzoate) using Thermomyces lanuginosus lipase (Lipozyme TLIM). The acylation reaction was optimized by varying the reaction medium, reaction temperature, acyl donor, substrate molar ratio, and reaction time. The highest conversion yield (76%) was obtained in tert-amyl alcohol (60 °C, 72 hr) using vinyl benzoate (molar ratio of 1:10) as acyl donor.

The effects of nuclear factor-kappa B in pancreatic stellate cells on inflammation and fibrosis of chronic pancreatitis.

The activation of pancreatic stellate cells (PSCs) plays a critical role in the progression of pancreatic fibrosis. Nuclear factor-kappa B (NF-κB) is associated with chronic pancreatitis (CP). Previous evidence indicated that NF-κB in acinar cells played a double-edged role upon pancreatic injury, whereas NF-κB in inflammatory cells promoted the progression of CP.

CircRNA expression profiles and function prediction in peripheral blood mononuclear cells of patients with acute ischemic stroke.

Most circular RNAs (circRNAs) belong to a novel class of noncoding RNAs that are produced by back-splicing reactions, and they regulate physiological and pathophysiological processes in human disease. Although circRNA expression has been shown to be altered in the ischemic cerebral tissue in animal studies, the expression profile of circRNA in the patients with acute ischemic stroke (AIS) has not been investigated to date. In this investigation, high-throughput sequencing was carried out to compare the circRNA expression of peripheral blood mononuclear cells (PBMCs) from five patients with AIS and five healthy subjects.

Safety and Feasibility of Repeated Intrathecal Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells in Patients with Neurological Diseases.

Mesenchymal stromal cells (MSCs) have become the most commonly used adult stem cells in regenerative medicine. Preclinical studies have shown that MSCs-based therapy is a potential new treatment approach for neurological diseases. Intrathecal injection has unique feature which allows stem cells to directly migrate to the lesion site in patients with central nervous system (CNS) diseases.

Intrathecal Injection of Allogenic Bone Marrow-Derived Mesenchymal Stromal Cells in Treatment of Patients with Severe Ischemic Stroke: Study Protocol for a Randomized Controlled Observer-Blinded Trial.

Mesenchymal stromal cells (MSCs) can differentiate into multiple tissues. Preclinical studies have shown that MSC-based therapy is a potential new treatment approach for ischemic stroke. These results support the urgent need for further studies of MSC transplantation in the treatment of ischemic stroke in humans.

The TLR9 Antagonist iCpG-ODN at Different Dosages Inhibits Cerebral Ischemia/Reperfusion Injury in Mice.

Background: Inflammatory responses are important mechanisms that are involved in cerebral ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate immune system, takes part in the inflammatory responses following cerebral I/R remains unclear.

Method: This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide (iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral artery occlusion.

Toll-Like Receptor 3 and Interferon β mRNA Expressions Were Increased in Peripheral Blood of Ischemic Stroke Patients with Good Outcome.

Background: Innate immunity plays an important role in brain ischemic injury, but there are only few studies on the effects of toll-like receptors (TLRs) on cerebral infarction patients up to now. We aimed to evaluate the TLR mRNA expression of patients with different outcomes.

Methods: Eighty-six cases suffering from cerebral infarction within 14 days were assigned into the good outcome group (n = 47) and the bad outcome group (n = 39) depending on the modified Rankin Scale scores (mRS ≤2 at 90 days following stroke onset was good outcome).