The leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor expressed on the majority of peripheral blood mononuclear cells and is important for the regulation of immune responses. The binding of LAIR-1 to its ligands results in the loss of immune function in the tumor microenvironment (TME) and a reduction in T cell function and immune responses of antigen-presenting cells. Using bioinformatics analysis, we showed that LAIR-1 is broadly upregulated in multiple types of cancer. By designing a LAIR-2-Fc recombinant protein to block the binding of LAIR-1 to its ligand collagen, we observed augmented cytotoxic T cell infiltration and function resulting in antitumor immune responses that eliminated cancer cells. Besides, LAIR-2-Fc fusion protein potentiated the antitumor effect of PD-1/L1 checkpoint blockade therapy. Collectively, our results support the targeting of LAIR-1 for potential immunotherapeutic applications.
Cefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against enteric Gram-negative bacilli such as Escherichia coli. We utilized a neutropenic mouse model of colibacillosis to examine the pharmacodynamic (PD) characteristics of cefquinome, as measured by organism number in homogenized thigh cultures after 24 h of therapy. Serum drug levels following 4-fold-escalating single doses of cefquinome were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic (PK) properties of cefquinome were linear over a dose range of 10 to 640 mg/kg of body weight. Serum half-lives ranged from 0.29 to 0.32 h. Dose fractionation studies over a 24-h dose range of 2.5 to 320 mg/kg were conducted every 3, 6, 12, or 24 h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. The free percentage of the dosing interval that the serum levels exceed the MIC (fT >MIC ) was the PK-PD index that best correlated with efficacy (R 2 ؍ 73% for E. coli, compared with 13% for the maximum concentration of the free drug in serum [fC max ]/MIC and 45% for the free-drug area under the concentration-time curve from 0 to 24 h [fAUC 0-24 ]/ MIC). Subsequently, we employed a similar dosing strategy by using 4-fold-increasing total cefquinome doses administered every 4 h to treat animals infected with four additional E. coli isolates. A sigmoid maximum-effect (E max ) model was used to estimate the magnitudes of the %fT >MIC associated with net bacterial stasis, a 1-log 10 CFU reduction from baseline, and a 2-log 10 CFU reduction from baseline; the corresponding values were 28.01% ؎ 2.27%, 37.23% ؎ 4.05%, and 51.69% ؎ 9.72%. The potent bactericidal activity makes cefquinome an attractive option for the treatment of infections caused by E. coli.
Grafting copolymers of polyacrylamide (PAM) with Konjac gum (KGM) have been synthesized using ceric-ion-induced initiation technique. The copolymers were characterized using several instrumental techniques, including infrared (IR) spectroscopy, elementary analysis, scanning electron microscopy (SEM), size exclusion chromatography (SEC) analysis, and intrinsic viscosity to confirm the success of grafting. The flocculation performance of graft copolymers was characterized by two methods. One was to study the relationship between the flocculants doses in kaolin suspension and the supernatant transmittance, and the other is to examine the time dependence of sediment height of kaolin suspensions. It was found that the graft copolymer is better than KGM and pure PAM. Biodegradation behavior was testified by monitoring the decay of relative viscosities, and approved by KGM ether bonds breaking in IR spectra and the molecule weight reduction in SEC analysis. The results indicate that the grafted KGM copolymers have improved both, flocculation performance and better biodegradable properties than the unmodified parent KGM and pure PAM.
Background/Aims: Insulinoma is a rare and potentially curable disease. It is often misdiagnosed as neurological or psychiatric disorder. This study was performed to characterize the neuropsychiatric symptoms (PNS) of the patients with insulinoma from a regional clinical center. Methods: All medical records of the patients with histopathologically identified insulinoma were reviewed during the period from 1998 to 2008. A case-control analysis was performed to compare the demographic data, details of clinical presentation, biochemical findings, tumor localization, and intraoperative findings between the patients with and without a prior misdiagnosis. Results: Among 42 patients with insulinoma, 25 patients with PNS were initially misdiagnosed as having a neurological or psychiatric disease, while 17 patients with no PNS were correctly diagnosed. Most (64%) of PNS cases were not diagnosed correctly until 12 months after the first consultation. In patients with PNS that remained undiagnosed for at least 5 years, the most frequent symptoms were confusion, convulsion, and visual disturbances. Twelve cases of PNS were initially misdiagnosed as epilepsy and 3 of them showed epileptiform discharges on electroencephalography. Conclusions: Episodic hypoglycemia induced by insulinoma can greatly mimic neurological and psychiatric presentation. A thorough history taking and inpatient assessment are necessary in evaluating recurrent neurological and psychiatric symptoms.
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