Opposed hemodynamic responses following increased excitation and parvalbumin-based inhibition

Understanding cellular contributions to hemodynamic activity is essential for interpreting blood-based brain mapping signals. Optogenetic studies examining cell-specific influences on local hemodynamics have reported that excitatory activity results in cerebral perfusion and blood volume increase, while inhibitory activity contributes to both vasodilation and vasoconstriction. How specific subpopulations of interneurons regulate the brain’s blood supply is less examined. Parvalbumin interneurons are the largest subpopulation of GABAergic neurons in the brain, critical for brain development, plasticity, and long-distance excitatory neurotransmission. Despite their essential role in brain function, the contribution of parvalbumin neurons to neurovascular coupling has been relatively unexamined. Using optical intrinsic signal imaging and laser speckle contrast imaging, we photostimulated awake and anesthetized transgenic mice expressing channelrhodopsin under a parvalbumin promoter. Increased parvalbumin activity reduced local oxygenation, cerebral blood volume, and cerebral blood flow. These “negative” hemodynamic responses were consistent within and across mice and reproducible across a broad range of photostimulus parameters. However, the sign and magnitude of the hemodynamic response resulting from increased parvalbumin activity depended on the type and level of anesthesia used. Opposed hemodynamic responses following increased excitation or parvalbumin-based inhibition suggest unique contributions from different cell populations to neurovascular coupling.     

Ventricular remodeling in growing rats with experimental diabetes: The impact of swimming training

Diabetic cardiomyopathy is associated with cardiac muscle remodeling, resulting in myocardial dysfunction, whereas exercise training (ET) is a useful nonpharmacological strategy for the therapy of cardiac diseases. This study tested the effects of low-intensity swimming-training on the structural remodeling of the left ventricle (LV) in growing rats with unmanaged experimental diabetes. Thirty-day-old male Wistar rats were divided into four groups (n = 5/group): sedentary-control (SC), exercised-control (EC), sedentary-diabetic (SD), and exercised-diabetic (ED). Swimming-training rats exercised 5 days/week, 90 min/day, with a load of 5% BW during 8 weeks. Sections of LV were stained with Periodic acid-Schiff, Sirius Red, and Gomori's reticulin. Seven days and 8 weeks after streptozotocin (STZ) induction (60 mg kg⁻¹ BW), blood glucose (BG) in the diabetic groups (SD = 581.40 ± 40.48; ED = 558.00 ± 48.89) was greater (p < 0.05) than in their controls (SC = 88.80 ± 21.70; EC = 85.60 ± 11.55). Swimming-training reduced BG by 23 mg/dL in the diabetics (p > 0.05). The LV of diabetic rats had increased interstitial collagen and reticular fibers on the extracellular matrix and presented glycogen accumulation. More importantly, all these adverse tissue changes induced by STZ were attenuated by ET. Together, these findings support the idea of a beneficial role of exercise in the LV remodeling in rats with unmanaged type-1 diabetes mellitus.     

Baicalein Inhibits DMBA/TPA-Induced Skin Tumorigenesis in Mice by Modulating Proliferation, Apoptosis, and Inflammation

Baicalein, one of the four major flavanoids extracted from the root of Scutellaria baicalensis, has been shown to exert chemopreventive effect against several cancers, including skin cancer. However, the precise mechanisms remain to be elucidated. In the present study, we investigated the chemopreventive activity of baicalein against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated skin tumorigenesis in C57BL/6 mice. We found that topical treatment with baicalein resulted in a significant inhibitory effect on DMBA/TPA-mediated tumor promotion. Furthermore, we observed that baicalein suppressed cell proliferation and promoted apoptosis in DMBA/TPA-mediated group. Additionally, pretreatment with baicalein inhibited the production of inflammatory cells in DMBA/TPA-induced skin/tumors. Further experiments showed that baicalein reduced TPA-induced skin hyperplasia as well as infiltration of polymorphonuclear leukocytes in the dermis. In conclusion, our data suggest that baicalein inhibits DMBA/TPA-induced skin tumorigenesis by suppressing proliferation and inflammation and promoting apoptosis.     

Sustained and differential antibody responses to virulence proteins of Brucella melitensis during acute and chronic infections in human brucellosis

Brucellosis is an important zoonotic disease caused primarily by the bacterial pathogens Brucella melitensis and B. abortus. The pathogens cause debilitating febrile illness that can progress into a long-lasting disease with severe complications in humans. Understanding the mechanisms by which the host immune system responds to the infection will provide important information on the pathogenesis and development of differential diagnostic assays. In this study, a protein microarray was used to evaluate the antibody responses of brucellosis patients at different infection stages. A total of 107 outer membrane proteins, surface-exposed or secreted proteins, and known or putative virulence-associated proteins of B. melitensis were successfully expressed in Escherichia coli and used to fabricate the protein microarray. Then, 99 serum samples from acute, chronic, primary infection, or relapse brucellosis patients were probed with the protein microarray. Antibodies to 66 of the proteins were detected at least in one serum sample. Among the antigens, the combination of BMEII0318, BMEII0513, BMEI0748, and BMEII1116 could be used as serodiagnostic antigens for brucellosis. Patients at different infection stages show distinct antibody profiles. The numbers of antibodies in the relapse patients were superior to those in the primary infection patients, and the response magnitude of antibodies in the chronic infection patients was higher than those in the acute brucellosis patients. The sustained and differential antibody profiles of patients at different infection stages have implications for the development of new serological methods for the accurate diagnosis of human brucellosis, and contribute to a more detailed understanding of the pathogenesis of chronic brucellosis.     

Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson''s trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.     

The Effect of Porphyromonas gingivalis Lipopolysaccharide on the Pyroptosis of Gingival Fibroblasts

Inflammation - Periodontitis is a chronic inflammatory disease induced by Porphyromonas gingivalis (P. gingivalis) and other pathogens. P. gingivalis release various virulence factors including...     

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa

ObjectivesAreas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso.MethodsIn a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens.ResultsA total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases.ConclusionsViral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.