ALPK1 signaling pathway activation by HMGB1 drives microglial pyroptosis and ferroptosis and brain injury after acute ischemic stroke.

Pyroptosis and ferroptosis emerge as remarkable contributors to neuronal death and inflammation following ischemic stroke. High mobility group box 1 (HMGB1), a principal damage-associated molecular pattern (DAMP), is implicated in pyroptosis and ferroptosis post-stroke. Our previous research has demonstrated that alpha kinase 1 (ALPK1), a novel cytoplasmic pattern recognition receptor (PRR), plays an important role in mediating inflammatory damage following ischemic stroke.

A novel therapeutic strategy for leukopenia: Miltefosine activates the Ras/MEK/ERK pathway to promote neutrophil differentiation.

Leukopenia, marked by diminished white blood cell (WBC) counts, presents significant challenges in the management of hematological malignancies and immunocompromised patients. This study evaluated the therapeutic potential of miltefosine (MFS), a phospholipid analogue, for treating leukopenia. In vitro studies using HL60 and NB4 cells revealed that MFS effectively promoted neutrophil differentiation and function, evidenced by the upregulation of surface markers CD11b, CD11c, CD14, and CD15, as well as enhanced bactericidal activity assessed through the NBT reduction assay.

Thonningianin A from Penthorum chinense Pursh as a targeted inhibitor of Alzheimer's disease-related β-amyloid and Tau proteins.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, β-amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression.

Mitophagy and cGAS-STING crosstalk in neuroinflammation.

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS-STING pathway, which is crucial for innate immunity. This pathway responds to mitochondrial DNA and is associated with cellular stress response.

Free total rhubarb anthraquinones protect intestinal mucosal barrier of SAP rats via inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

Ethnopharmacological Relevance: Rhubarb is the peeled and dried roots of Rheum palmatum L. and Rheum tanguticum Maxim. ex Balf.

Poly (ADP-ribose) polymerase 1 and neurodegenerative diseases: Past, present, and future.

Poly (ADP-ribose) polymerase 1 (PARP1) is a first responder that recognizes DNA damage and facilitates its repair. Neurodegenerative diseases, characterized by progressive neuron loss driven by various risk factors, including DNA damage, have increasingly shed light on the pivotal involvement of PARP1. During the early phases of neurodegenerative diseases, PARP1 experiences controlled activation to swiftly address mild DNA damage, thereby contributing to maintain brain homeostasis.

Stress-enhanced cardiac lncRNA Morrbid protects hearts from acute myocardial infarction.

Myeloid RNA regulator of Bim-induced death (Morrbid) is a newly identified leukocyte-specific long noncoding RNA (lncRNA). However, the expression and biological functions of Morrbid in cardiomyocytes and heart disease are currently unclear. This study was meant to determine the role of cardiac Morrbid in acute myocardial infarction (AMI) and to identify the potential cellular and molecular mechanisms involved.

Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of asparagus against polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age that still lacks effective treatment. Inflammation is one of the important features of PCOS. Asparagus (ASP) has anti-inflammatory, antioxidant, and anti-aging pharmacological effects, and its anti-tumor effects have been demonstrated in a variety of tumors.

Micelle encapsulation zinc-doped copper oxide nanocomposites reverse Olaparib resistance in ovarian cancer by disrupting homologous recombination repair.

Micelle Encapsulation Zinc-doped copper oxide nanocomposites (MEnZn-CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn-CuO NPs) using non-micellar beam. Compared with Zn-CuO NPs, MEnZn-CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn-CuO NPs on human ovarian cancer cells.

Curcumin-Loaded Platelet Membrane Bioinspired Chitosan-Modified Liposome for Effective Cancer Therapy.

Cancer is a serious threat to human health, and chemotherapy for cancer is limited by severe side effects. Curcumin (CUR) is a commonly used natural product for antitumor treatment without safety concerns. However, low bioavailability and poor tumor accumulation are great obstacles for its clinical application.

Ferredoxin 1 regulates granulosa cell apoptosis and autophagy in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common reproductive endocrine disorder in women of reproductive age, causes anovulatory infertility. Increased apoptosis of granulosa cells has been identified as one of the key factors contributing to abnormal follicular development. Ferredoxin 1 (FDX1) encodes a small ferredoxin that is involved in the reduction in mitochondrial cytochromes and the synthesis of various steroid hormones and has the potential to influence the function of granulosa cells.

Integrated bioinformatics analysis and screening of hub genes in polycystic ovary syndrome.

Purpose: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders, posing a serious threat to the health of women. Herein, we aimed to explore new biomarkers and potential therapeutic targets for PCOS by employing integrated bioinformatics tools.

Methods: Three gene expression profile datasets (GSE138518, GSE155489, GSE106724) were obtained from the Gene Expression Omnibus database and the differentially expressed genes in PCOS and normal groups with an adjusted p-value < 0.

High-throughput screening for amyloid- binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC-DAD-Q/TOF-MS/MS.

Discovery of drugs rapidly and effectively is an important aspect for Alzheimer's disease (AD). In this study, a novel high-throughput screening (HTS) method aims at screening the small-molecules with amyloid- (A) binding affinity from natural medicines, based on the combinational use of biolayer interferometry (BLI) and ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time-of-flight tandem mass spectrometry (UHPLC-DAD-Q/TOF-MS/MS) has been firstly developed. Briefly, the components in natural medicines disassociated from biotinylated A were collected to analyze their potential A binding affinity by UHPLC-DAD-Q/TOF-MS/MS.

Dynamic Monitoring of Immunoinflammatory Response Identifies Immunoswitching Characteristics of Severe Acute Pancreatitis in Rats.

Background: Immune dysfunction is the main characteristic of severe acute pancreatitis (SAP), and the timing of immune regulation has become a major challenge for SAP treatment. Previous reports about the time point at which the immune status of SAP changed from excessive inflammatory response to immunosuppression (hypo-inflammatory response) are conflicting.

Purposes: The aims of this study are to explore the immunological dynamic changes in SAP rats from the perspective of intestinal mucosal immune function, and to determine the immunoswitching point from excessive inflammatory response to immunosuppression.

A PETAR method for risk assessment of human health and environment on the regional scale.

Risk assessments are necessary to effectively reveal the state of the degradation of living environments on a regional scale. However, risk assessments are often limited by time, cost, and technology, which make conducting effective evaluations difficult. Thus, in this study, the procedure for ecological tiered assessment of risk (PETAR) method was used to analyze the human health and environmental risks in Daye, China.

Protein kinases as therapeutic targets to develop anticancer drugs with natural alkaloids.

: Protein kinases play an important role in cell proliferation, differentiation, mobility and cell cycle arrest etc. These enzymes act as important targets in developing anticancer agents. Over the years, a large number of protein kinase inhibitors have been discovered and developed as anticancer agents for the treatment of cancers clinically.

Alnustone inhibits the growth of hepatocellular carcinoma via ROS- mediated PI3K/Akt/mTOR/p70S6K axis.

Alnustone, a diarylheptane compound, exhibits potent growth inhibition against hepatocellular carcinoma (HCC) BEL-7402 cells. However, the underlying mechanisms associated with its anticancer activity remain unknown. In the present study, we evaluated the anticancer effect of alnustone against several human cancers focused on HCC and the possible associated mechanisms.

Enolase 1, a Moonlighting Protein, as a Potential Target for Cancer Treatment.

Enolase 1 (ENO1) is a moonlighting protein, function as a glycolysis enzyme, a plasminogen receptor and a DNA binding protein. ENO1 play an important role in the process of cancer development. The transcription, translation, post-translational modifying activities and the immunoregulatory role of ENO1 at the cancer development is receiving increasing attention.

Mere15, a novel polypeptide from Meretrix meretrix, inhibits proliferation and metastasis of human non-small cell lung cancer cells through regulating the PI3K/Akt/mTOR signaling pathway.

Mere15, an anticancer polypeptide with a molecular weight of 15 kDa, is extracted from the marine species Meretrix meretrix. A previous study in our laboratory has confirmed that Mere15 displays a potent antitumor activity. However, the underlying mechanism of Mere15 still remains unclear.

Rapid Screening and Characterization of Triterpene Saponins from the Root of Phytolacca acinosa Roxb by High-Performance Liquid Chromatography Coupled to Electrospray Ionization and Quadrupole Time-of-Flight Mass Spectrometry.

Triterpene saponins (TSs) are important bioactive constituents with structural diversity widely distributed in many plants. The root of Phytolacca acinosa Roxb (RPa) has been used as a traditional Chinese medicine. However, TSs as the main active ingredients in RPa have not been fully characterized.

Targeting microglial autophagic degradation in NLRP3 inflammasome-mediated neurodegenerative diseases.

Neuroinflammation is considered as a detrimental factor in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), etc. Nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3), the most well-studied inflammasome, is abundantly expressed in microglia and has gained considerable attention. Misfolded proteins are characterized as the common hallmarks of neurodegenerative diseases due to not only their induced neuronal toxicity but also their effects in over-activating microglia and the NLRP3 inflammasome.

Protein kinases as targets for developing anticancer agents from marine organisms.

Protein kinases play a fundamental role in the intracellular transduction because of their ability to phosphorylate plethora of proteins. Over the past three decades, numerous protein kinase inhibitors have been identified and are being used clinically successfully. The biodiversity of marine organisms provides a rich source for the discovery and development of novel anticancer agents in the treatment of human malignancies and a lot of bioactive ingredients from marine organisms display anticancer effects by affecting the protein kinases-mediated pathways.

Exosomes-Coated miR-34a Displays Potent Antitumor Activity in Pancreatic Cancer Both in vitro and in vivo.

Purpose: MiR-34a, which acts as an important tumor suppressor gene, plays an important role in pancreatic cancer. However, the therapeutic application of miR-34a is limited by the lack of an effective delivery system. In the present study, we synthesize exosomes-coated miR-34a (exomiR-34a), and the anticancer effect of exomiR-34a was evaluated in pancreatic cancer.

Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer.

Enzalutamide, an androgen receptor inhibitor, has been clinically approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in the United States. However, patients only benefit from enzalutamide for a short period of time as resistance may develop. Therefore, it is vital to develop a novel strategy to overcome enzalutamide resistance.

Exosomes-coated bcl-2 siRNA inhibits the growth of digestive system tumors both in vitro and in vivo.

Background: The therapeutic application of small interfering RNA is limited by the lack of an effective delivery system to tumors. In the present study, an efficient approach to deliver siRNA to cancer cells using exosome system was developed.

Materials & Methods: Exosomes were isolated from bovine milk and exosomes-coated bcl-2 siRNA (exosiBcl-2) was synthesized using ultrasonic approach.