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Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic Bartonella and Rickettsia species are known to infect the most common flea infesting cats and dogs worldwide: Ctenocephalides felis, the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored. We aimed to determine cat host and flea factors independently associated with flea Bartonella and Rickettsia infection. We also assessed flea and cat infection by flea-host pair and location. To accomplish these aims, we performed qPCR for the detection of Bartonella, hemotropic Mycoplasma, Rickettsia, and Wolbachia DNA using paired cat and flea samples obtained from free-roaming cats presenting for spay or neuter across four locations in the United States. A logistic regression model was employed to identify the effect of cat (sex, body weight, geographic location, and Bartonella, hemotropic Mycoplasma, and Rickettsia spp., infection) and flea (clade and Rickettsia and Wolbachia infection) factors on C. felis Bartonella clarridgeiae infection. From 189 free roaming cats, we collected 84 fleas: Ctenocephalides felis (78/84), Cediopsylla simplex (4/84), Orchopeas howardi (1/84), and Nosopsyllus fasciatus (1/84). Ctenocephalides felis were phylogenetically assigned to Clades 1, 4, and 6 by cox1 gene amplification. Rickettsia asembonensis (52/84) and B. clarridgeiae (16/84) were the most common pathogenic bacteria detected in fleas. Our model identified host cat sex and weight as independently associated with B. clarridgeiae infection in fleas. Rickettsia asembonensis (52/84), Rickettsia felis (7/84) and Bartonella henselae (7/84) were detected in specific clades: R. felis was detected only in Clades 1 and 6 while B. henselae and R. asembonensis were detected only in Clade 4. Wolbachia spp., also displayed clade specificity with strains other than Wolbachia wCfeT only infecting fleas from Clade 6. There was poor flea and host agreement for Bartonella spp., infection; however, there was agreement in the Bartonella species detected in cats and fleas by geographic location. These findings reinforce the importance of considering reservoir host attributes and vector phylogenetic diversity in epidemiological studies of flea-borne pathogens. Widespread sampling is necessary to identify the factors driving flea-borne pathogen presence and transmission.

Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic Bartonella and Rickettsia species are known to infect the most common flea infesting cats and dogs worldwide: Ctenocephalides felis, the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored. We aimed to determine cat host and flea factors independently associated with flea Bartonella and Rickettsia infection. We also assessed flea and cat infection by flea-host pair and location. To accomplish these aims, we performed qPCR for the detection of Bartonella, hemotropic Mycoplasma, Rickettsia, and Wolbachia DNA using paired cat and flea samples obtained from free-roaming cats presenting for spay or neuter across four locations in the United States. A logistic regression model was employed to identify the effect of cat (sex, body weight, geographic location, and Bartonella, hemotropic Mycoplasma, and Rickettsia spp., infection) and flea (clade and Rickettsia and Wolbachia infection) factors on C. felis Bartonella clarridgeiae infection. From 189 free roaming cats, we collected 84 fleas: Ctenocephalides felis (78/84), Cediopsylla simplex (4/84), Orchopeas howardi (1/84), and Nosopsyllus fasciatus (1/84). Ctenocephalides felis were phylogenetically assigned to Clades 1, 4, and 6 by cox1 gene amplification. Rickettsia asembonensis (52/84) and B. clarridgeiae (16/84) were the most common pathogenic bacteria detected in fleas. Our model identified host cat sex and weight as independently associated with B. clarridgeiae infection in fleas. Rickettsia asembonensis (52/84), Rickettsia felis (7/84) and Bartonella henselae (7/84) were detected in specific clades: R. felis was detected only in Clades 1 and 6 while B. henselae and R. asembonensis were detected only in Clade 4. Wolbachia spp., also displayed clade specificity with strains other than Wolbachia wCfeT only infecting fleas from Clade 6. There was poor flea and host agreement for Bartonella spp., infection; however, there was agreement in the Bartonella species detected in cats and fleas by geographic location. These findings reinforce the importance of considering reservoir host attributes and vector phylogenetic diversity in epidemiological studies of fleaborne pathogens. Widespread sampling is necessary to identify the factors driving flea-borne pathogen presence and transmission. [ABSTRACT FROM AUTHOR]

Polymethoxyflavonoids (PMFs), the main bioactive compounds naturally occurring in the pericarp of Citrus reticulata ‘Chachi’ (CRCP), possess significant antitumor action. However, the action of PMFs in nasopharyngeal carcinoma (NPC) is currently unknown. The present research study was conducted to investigate the inhibitory mechanisms of PMFs from CRCP on NPC growth in vivo and in vitro. In our research, we used high-speed counter-current chromatography (HSCCC) to separate four PMFs (nobiletin (NOB), 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), tangeretin (TGN), and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)) from CRCP. CCK-8 assay was used to preliminarily screen cell viability following exposure to the four PMFs. Colony formation, Hoechst-33258 staining, transwell, and wound scratch assays were performed to assess the anti-proliferation, invasion, migration, and apoptosis-inducing effects of HMF on NPC cells. NPC tumors in xenograft tumor transplantation experiments were also established to explore the effect of HMF (100 and 150 mg/kg/day) on NPC. The histopathological changes in the treated rats were observed by H&E staining and Ki-67 detection by immunohistochemical techniques. The expressions of P70S6K, p-P70S6K, S6, p-S6, COX-2, p53, and p-p53 were measured by Western blot. The four PMFs were obtained with high purity (>95.0%). The results of the preliminary screening by CCK-8 assay suggested that HMF had the strongest inhibitory effect on NPC cell growth. The results of the colony formation, Hoechst-33258 staining, transwell, and wound scratch assays indicated that HMF had significant anti-proliferation, invasion, migration, and apoptosis-inducing ability in NPC cells. Moreover, HMF suppressed NPC tumor growth in xenograft tumor transplantation experiments. Further investigation suggested that HMF regulated NPC cells proliferation, apoptosis, migration, and invasion by activating AMPK-dependent signaling pathways. In conclusion, HMF-induced AMPK activation inhibited NPC cell growth, invasion, and metastatic potency by downregulating the activation of the mTOR signaling pathway and COX-2 protein levels, as well as enhancing the p53 phosphorylation level. Our study provides a crucial experimental basis for the clinical treatment of NPC, as well as the development and utilization of PMFs from CRCP.

ObjectivesTo evaluate the implementation effect of hepatitis C medical insurance reimbursement policy in China from the view of medical institutions.MethodsThe electronic medical record of a top tertiary hospital in Chengdu from January 2014 to December 2020 were extracted, and the interrupted time series model was used to analyze the changes in diagnosis and treatment behavior and disease burden of hepatitis C patients after the implementation of HCV insurance reimbursement policy.ResultsIn terms of diagnosis and treatment, the number of visits (β2 = 19.290, P < 0.001) and treatments (β2 = 14.291, P < 0.01) increased instantaneously after the implementation of the outpatient reimbursement policy in Chengdu in 2018, and there was no significant change after the implementation of the single line payment policy for oral direct antiviral (DAA) drugs in 2019 (P > 0.05); in terms of medical expenses, the total treatment cost (β2 = 21439.3, P < 0.001), out-of-pocket expenses (β2 = 6109.44, P < 0.001) and drug expenses (β2 = 21889.8, P < 0.001) of hepatitis C patients have been significantly reduced after the implementation of the single-line payment policy.ConclusionHepatitis C medical insurance reimbursement policy can promote hepatitis C patients to actively seek medical treatment, promote the widespread use of DAA scheme, reduce the burden of patients, and improve the treatment efficiency of hepatitis C.

Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set up a mouse model of sciatic nerve injury (SNI) and conducted an unbiased, quantitative proteomic study followed by biochemical assays to confirm some of the changed proteins. Among them, the protein levels of ADP-dependent glucokinase (ADPGK) were significantly increased in the injured sciatic nerve. Further examination indicated that ADPGK was specifically expressed and upregulated in macrophages but not neurons or Schwann cells upon injury. Furthermore, culturing immortalized bone marrow-derived macrophages (iBMDMs) in vitro with the conditioned media from transected axons of mouse dorsal root ganglion (DRG) neurons induced ADPGK upregulation in iBMDMs, suggesting that injured axons could promote ADPGK expression in macrophages non-cell autonomously. Finally, we showed that overexpression of ADPGK per se did not activate macrophages but promoted the phagocytotic activity of lipopolysaccharides (LPS)-treated macrophages. Together, this proteomic analysis reveals interesting changes of many proteins within the injured nerve and our data identify ADPGK as an important in vivo booster of injury-induced macrophage phagocytosis.

Recently, drug delivery vehicles based on nanotechnology have significantly attracted the attention of researchers in the field of nanomedicine since they can achieve ideal drug release and biodistribution. Among the various organic or inorganic materials that used to prepare drug delivery vehicles for effective cancer treatment, serum albumin-based nanovehicles have been widely developed and investigated due to their prominent superiorities, including good biocompatibility, high stability, nontoxicity, non-immunogenicity, easy preparation, and functionalization, allowing them to be promising candidates for cancer diagnosis and therapy. This article reviews the recent advances on the applications of serum albumin-based nanovehicles in cancer diagnosis and therapy. We first introduce the essential information of bovine serum albumin (BSA) and human serum albumin (HSA), and discuss their drug loading strategies. We then discuss the different types of serum albumin-based nanovehicles including albumin nanoparticles, surface-functionalized albumin nanoparticles, and albumin nanocomplexes. Moreover, after briefly discussing the application of serum albumin-based nanovehicles used as the nanoprobes in cancer diagnosis, we also describe the serum albumin-based nanovehicle-assisted cancer theranostics, involving gas therapy, chemodynamic therapy (CDT), phototherapy (PTT/PDT), sonodynamic therapy (SDT), and other therapies as well as cancer imaging. Numerous studies cited in our review show that serum albumin-based nanovehicles possess a great potential in cancer diagnostic and therapeutic applications.

Adiponectin, a cytokine secreted by mature adipocytes, proves to be neuroprotective. We have previously reported that running triggers adiponectin up-regulation which subsequently promotes generation of hippocampal neurons and thereby alleviates depression-like behaviors in non-stressed mice. However, under the stressing condition, whether adiponectin could still exert antidepressant-like effects following exercise remained unexplored. In this study, by means of repeated corticosterone injections to mimic stress insult and voluntary wheel running as physical exercise intervention, we examined whether exercise-elicited antidepressive effects might involve adiponectin’s regulation on hippocampal neurogenesis and dendritic plasticity in stressed mice. Here we show that repeated injections of corticosterone inhibited hippocampal neurogenesis and impaired dendritic morphology of neurons in the dentate gyrus of both wild-type and adiponectin-knockout mice comparably, which subsequently evoked depression-like behaviors. Voluntary wheel running attenuated corticosterone-suppressed neurogenesis and enhanced dendritic plasticity in the hippocampus, ultimately reducing depression-like behaviors in wild-type, but not adiponectin-knockout mice. We further demonstrate that such proneurogenic effects were potentially achieved through activation of the AMP-dependent kinase (AMPK) pathway. Our study provides the first evidence that adiponectin signaling is essential for physical exercise-triggered effects on stress-elicited depression by retaining the normal proliferation of neural progenitors and dendritic morphology of neurons in the hippocampal dentate gyrus, which may depend on activation of the AMPK pathway.

Intelligent drug delivery systems based on nanotechnology have been widely developed and investigated in the field of nanomedicine since they were able to maximize the therapeutic efficacy and minimize the undesirable adverse effects. Among a variety of organic or inorganic nanomaterials available to fabricate drug delivery systems (DDSs) for cancer therapy and diagnosis, poly(D,L-lactic-co-glycolic acid) (PLGA) has been extensively employed due to its biocompatibility and biodegradability. In this paper, we review the recent status of research on the application of PLGA-based drug delivery systems (DDSs) in remotely triggered cancer therapy and the strategies for tumor imaging provided by PLGA-based DDSs. We firstly discuss the employment of PLGA-based DDSs for remotely triggered cancer therapy, including photo-triggered, ultrasound-triggered, magnetic field-triggered, and radiofrequency-triggered cancer therapy. Photo-triggered cancer therapy involves photodynamic therapy (PDT), photothermal therapy (PTT), and photo-triggered chemotherapeutics release. Ultrasound-triggered cancer therapy involves high intensity focused ultrasound (HIFU) treatment, ultrasound-triggered chemotherapeutics release, and ultrasound-enhanced efficiency of gene transfection. The strategies which endows PLGA-based DDSs with imaging properties and the PLGA-based cancer theranostics are further discussed. Additionally, we also discuss the targeting strategies which provide PLGA-based DDSs with passive, active or magnetic tumor-targeting abilities. Numerous studies cited in our review demonstrate the great potential of PLGA-based DDSs as effective theranostic agent for cancer therapy and diagnosis.

Research of nanotechnology for cancer therapy and diagnosis extends beyond drug delivery into the targeted site or surveillance the distribution of nanodrugs in vivo or distinction tumor tissue from normal tissue. To satisfy the clinic needs, nanotheranostic platform should hide the surveillance by immune system and the sequestration by filtration organs (i.e., liver and spleen). Use of biologically derived cellular components in the fabrication of nanoparticles can hide these barriers. In this review, we update the recent progress on cell membrane-coated nanoparticles for cancer theranostics. We hope this review paper can inspire further innovations in biomimetic nanomedicine.