Novel tripeptide RKH derived from protects against lethal sepsis.

Objective: The pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality. (AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development.

Anaplasma phagocytophilum Hijacks Flotillin and NPC1 Complex To Acquire Intracellular Cholesterol for Proliferation, Which Can Be Inhibited with Ezetimibe.

The intracellular cholesterol transport protein Niemann-Pick type C1 (NPC1) and lipid-raft protein flotillin (FLOT) are required for cholesterol uptake by the obligatory intracellular bacterium Anaplasma phagocytophilum and for infection, and each protein localizes to membrane-bound inclusions containing replicating bacteria. Here, we found striking localization of FLOT2 in NPC1-lined vesicles and a physical interaction between FLOT2 and NPC1. This interaction was cholesterol dependent, as a CRAC (cholesterol recognition/interaction amino acid cholesterol-binding) domain mutant of FLOT2 did not interact with NPC1, and the cholesterol-sequestering agent methyl-β-cyclodextrin reduced the interaction.

Chemotherapy-induced peripheral neuropathy is promoted by enhanced spinal insulin-like growth factor-1 levels via astrocyte-dependent mechanisms.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and intractable complication in chemotherapy-receiving patients. Insulin-like growth factor-1 (IGF-1) is a popular neurotrophin with various functions, such as maintaining neuronal survival and synaptic functioning in the central nervous system. Therefore, we hypothesized that the IGF-1 signaling pathway could be a candidate target for treating CIPN.

Abnormal Insulin-like Growth Factor 1 Signaling Regulates Neuropathic Pain by Mediating the Mechanistic Target of Rapamycin-Related Autophagy and Neuroinflammation in Mice.

Neuropathic pain is a chronic condition with little specific treatment. Insulin-like growth factor 1 (IGF1), interacting with its receptor, IGF1R, serves a vital role in neuronal and brain functions such as autophagy and neuroinflammation. Yet, the function of spinal IGF1/IGF1R in neuropathic pain is unclear.

Potomac horse fever in Ontario: Clinical, geographic, and diagnostic aspects.

Clinical findings, geographic locations, laboratory diagnoses, and culture isolation of spp. in Potomac horse fever (PHF) cases diagnosed in Ontario between 2015 and 2019 are described. Forty-six confirmed PHF cases occurred from late June to early September.

Self-supported nickel-doped molybdenum carbide nanoflower clusters on carbon fiber paper for an efficient hydrogen evolution reaction.

Developing an efficient, stable and low-cost noble-metal-free electrocatalyst for the hydrogen evolution reaction (HER) is an effective way to alleviate the energy crisis. Herein, we report a simple and facile approach to synthesize self-supported Ni-doped MoC via a molten salt method. By optimizing the content of Ni, the concentration of Ni(NO), and the annealing time, self-supported nanoflower-like electrocatalysts composed of ultrathin nanosheets on carbon fiber paper (CFP) can be achieved.

Comparative Analysis of Genome of Ehrlichia sp. HF, a Model Bacterium to Study Fatal Human Ehrlichiosis.

Background: The genus Ehrlichia consists of tick-borne obligatory intracellular bacteria that can cause deadly diseases of medical and agricultural importance. Ehrlichia sp. HF, isolated from Ixodes ovatus ticks in Japan [also referred to as I.

β-SiN Microcrystals Prepared by Carbothermal Reduction-Nitridation of Quartz.

Single phase β-SiN with microcrystals was synthesized via carbothermal reduction-nitridation (CRN) of quartz and carbon coke powder as starting materials. The effects of reaction parameters, i.e.

mTOR activation due to APPL1 deficiency exacerbates hyperalgesia via Rab5/Akt and AMPK signaling pathway in streptozocin-induced diabetic rats.

Painful diabetic neuropathy is a common complication of diabetes mellitus with obscure underlying mechanisms. The adaptor protein APPL1 is critical in mediating the insulin sensitizing and insulin signaling. In neurons, APPL1 reportedly affects synaptic plasticity, while its role in the pathogenesis of painful diabetic neuropathy is masked.

Micro-Nano Carbon Structures with Platelet, Glassy and Tube-Like Morphologies.

Carbon source precursors for high-grade, clean, and low-carbon refractories were obtained by in situ exfoliation of flake graphite (FG) and phenol-formaldehyde resin (PF) composites with three-roll milling (TRM) for the fabrication of graphite nanoplatelets. In addition, by using Ni(NO)·6HO as a catalyst in the pyrolysis process, multidimensional carbon nanostructures were obtained with coexisting graphite nanoplatelets (GNPs), glassy carbon (GC), and carbon nanotubes (CNTs). The resulting GNPs (exfoliated 16 times) had sizes of 10-30 μm, thicknesses of 30-50 nm, and could be uniformly dispersed in GC from the PF pyrolysis.

Infection by Anaplasma phagocytophilum Requires Recruitment of Low-Density Lipoprotein Cholesterol by Flotillins.

is an obligatory intracellular bacterium that proliferates in membrane-bound inclusions. is dependent on cholesterol and acquire cholesterol from low-density lipoprotein (LDL) endocytosed by mammalian host cells. The mechanism of cholesterol transport to inclusions, however, is not fully understood.

Contributions of mTOR Activation-Mediated Upregulation of Synapsin II and Neurite Outgrowth to Hyperalgesia in STZ-Induced Diabetic Rats.

Painful diabetic neuropathy (PDN) is among the common complications in diabetes mellitus (DM), with its underlying mechanisms largely unknown. Synapsin II is primarily expressed in the spinal dorsal horn, and its upregulation mediates a superfluous release of glutamate and a deficiency of GABAergic interneuron synaptic transmission, which is directly implicated in the facilitation of pain signals in the hyperalgesic nociceptive response. Recently, synapsin II has been revealed to be associated with the modulation of neurite outgrowth, whereas the process of this neuronal structural neuroplasticity following neuronal hyperexcitability still remains unclear.

Effect of the spinal apelin‑APJ system on the pathogenesis of chronic constriction injury‑induced neuropathic pain in rats.

Apelin is hypothesized to serve a dual function in pain processing. Spinal administration of apelin induces hyperalgesia, while opioid receptors are implicated in the antinociceptive effects of apelin in acute nociceptive models. However, whether the apelin‑apelin receptor (APJ) system is involved in neuropathic pain remains to be elucidated.

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.

Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein.

Reversal of TRESK Downregulation Alleviates Neuropathic Pain by Inhibiting Activation of Gliocytes in the Spinal Cord.

Despite the consensus that activation of TWIK-related spinal cord K (TRESK) might contribute to the pathogenesis of chronic pain, the specific mechanisms underlying the transfer and development of pain signals still remain obscure. In the present study, we validated that TRESK was expressed in neurons instead of glial cells. Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately.

Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase.

Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth.

An Ecotype of Neorickettsia risticii Causing Potomac Horse Fever in Canada.

Unlabelled: Neorickettsia (formerly Ehrlichia) risticii is an obligatory intracellular bacterium of digenetic trematodes. When a horse accidentally ingests aquatic insects containing encysted trematodes infected with N. risticii, the bacterium is transmitted from trematodes to horse cells and causes an acute and often fatal disease called Potomac horse fever (PHF).

Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.

The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.

EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin.

Unlabelled: Obligate intracellular bacteria, such as Ehrlichia chaffeensis, perish unless they can enter eukaryotic cells. E. chaffeensis is the etiological agent of human monocytic ehrlichiosis, an emerging infectious disease.

The Protective Effect of Stauntonia Chinensis Polysaccharide on CCl4-induced Acute Liver Injuries in Mice.

Objective: To investigate the protective effect of Stauntonia chinensis polysaccharides (SCP) on carbon tetrachloride (CCl4) induced acute liver injuries in mice.

Methods: KUNMING MICE WERE RANDOMLY DIVIDED INTO THREE GROUPS: the control group, the pathological model group, and the SCP group. The SCP group was further divided into three subgroups based on SCP treatment: Low dosage (50 mg/kg), medium dosage (100 mg/kg) and high dosage (200 mg/kg).

Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection.

Autophagy, a cytoplasmic catabolic process, plays a critical role in defense against intracellular infection. In turn, evasion or inhibition of autophagy has emerged as an important virulence factor for intracellular pathogens. However, Anaplasma phagocytophilum, the obligatory intracellular bacterium that causes human granulocytic anaplasmosis, replicates in the membrane-bound compartment resembling early autophagosome.

Subversion of NPC1 pathway of cholesterol transport by Anaplasma phagocytophilum.

Intracellular cholesterol amounts, distribution and traffic are tightly regulated to maintain the healthy eukaryotic cell function. However, how intracellular pathogens that require cholesterol, interact with the host cholesterol homeostasis and traffic is not well understood. Anaplasma phagocytophilum is an obligatory intracellular and cholesterol-robbing bacterium, which causes human granulocytic anaplasmosis.

The prenylation inhibitor manumycin A reduces the viability of Anaplasma phagocytophilum.

Anaplasma phagocytophilum is an obligately intracellular bacterium and is the causative agent of human granulocytic anaplasmosis (HGA), an emerging and major tick-borne disease in the USA and other parts of the world. This study showed that the prenylation inhibitor manumycin A effectively blocked A. phagocytophilum infection in host cells (HL-60 or RF/6A cells).

Evaluation of peptide- and recombinant protein-based assays for detection of anti-Ehrlichia ewingii antibodies in experimentally and naturally infected dogs. [corrected].

Objective: To evaluate microtiter-plate format ELISAs constructed by use of different diagnostic targets derived from the Ehrlichia ewingii p28 outer membrane protein for detection of E ewingii antibodies in experimentally and naturally infected dogs.

Sample Population: Serum samples from 87 kenneled dogs, 9 dogs experimentally infected with anti-E ewingii, and 180 potentially naturally exposed dogs from Missouri.

Procedures: The capacities of the synthetic peptide and truncated recombinant protein to function as detection reagents in ELISAs were compared by use of PCR assay, western blot analysis, and a full-length recombinant protein ELISA.