[Idiopathic pulmonary fibrosis: Desperately seeking a model]. / Fibrose pulmonaire idiopathique : recherche modèle désespérément.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of which the origin and development mechanisms remain unknown. The few available pharmacological treatments can only slow the progression of the disease. The development of curative treatments is hampered by the absence of experimental models that can mimic the specific pathophysiological mechanisms of IPF. The aim of this mini-review is to provide an overview of the most commonly used experimental animal models in the study of IPF and to underline the urgent need to seek out new, more satisfactory models.

Effectiveness of radiotherapy and targeted radionuclide therapy for melanoma in preclinical mouse models: A combination treatments overview.

Cutaneous melanoma is an aggressive and highly metastatic skin cancer. In recent years, immunotherapy and targeted small-molecule inhibitors have improved the overall survival of patients. Unfortunately, most patients in advanced stages of disease exhibit either intrinsically resistant or rapidly acquire resistance to these approved treatments. However, combination treatments have emerged to overcome resistance, and novel treatments based on radiotherapy (RT) and targeted radionuclide therapy (TRT) have been developed to treat melanoma in the preclinical mouse model, raising the question of whether synergy in combination therapies may motivate and increase their use as primary treatments for melanoma. To help clarify this question, we reviewed the studies in preclinical mouse models where they evaluated RT and TRT in combination with other approved and unapproved therapies from 2016 onwards, focusing on the type of melanoma model used (primary tumor and or metastatic model). PubMed® was the database in which the search was performed using mesh search algorithms resulting in 41 studies that comply with the inclusion rules of screening. Studies reviewed showed that synergy with RT or TRT had strong antitumor effects, such as tumor growth inhibition and fewer metastases, also exhibiting systemic protection. In addition, most studies were carried out on antitumor response for the implanted primary tumor, demonstrating that more studies are needed to evaluate these combined treatments in metastatic models on long-term protocols.

Antihyperglycemic activity of nanoemulsion of brown algae (Sargassum sp.). Ethanol extract in glucose tolerance test in male mice.

Nanoemulsion technology has been widely developed and applied to extracts of natural materials to enhance bioavailability and medicinal effects. This study aimed to determine the effectiveness of the Sargassum sp. ethanol extract nanoemulsions as an antihyperglycemic agent against fasting blood glucose levels in mice. The nanoemulsion formulation used Sargassum sp. extract and some additional ingredients, including chitosan, sodium tripolyphosphate, and tween 80. The antihyperglycemic test consisted of four groups, which were randomly selected. Treatment group (I) was given a nanoemulsion base without algae extract with a volume of 0.2mL/20gramBW; treatment group (II) was given glibenclamide at a dose of 0.52mg/20gramBW in 0.5% carboxymethylcellulose sodium (NaCMC) suspension with a volume of 0.2mL/20gramBW; treatment group (III) was given Sargassum sp. ethanol extract at a dose of 0.66mg/20 gramBW in 0.5% Na CMC suspension with a volume of 0.2mL/20gramBW; the treatment group (IV) was given formula of nanoemulsions of ethanol extract Sargassum sp with a volume of 0.2mL/20gramBW equivalent to a dose concentration Sargassum sp. ethanol extract of 0.66mg/20gramBW. The size of the nanoemulsion particles of the Sargassum sp. extract was 341.5-296.5nm with a zeta potential of 19.4-16.9mv. Treatment group (II) had the same antihyperglycemic effect as treatment group (IV). In contrast, treatment groups (I) and (III) had a relatively lower antihyperglycemic effect. This suggests that the Sargassum sp. extract nanoemulsion formula can be used as an alternative antihyperglycemic agent.

Pilot study of jadomycin B pharmacokinetics and anti-tumoral effects in zebrafish larvae and mouse breast cancer xenograft models.

Despite numerous therapeutic options, multidrug resistance (MDR) remains an obstacle to successful breast cancer therapy. Jadomycin B, a natural product derived from Streptomyces venezuelae ISP5230, maintains cytotoxicity in MDR human breast cancer cells. Our objectives were to evaluate the pharmacokinetics, toxicity, anti-tumoral, and anti-metastatic effects of jadomycin B in zebrafish larvae and mice. In a zebrafish larval xenograft model, jadomycin B significantly reduced the proliferation of human MDA-MB-231 cells at or below its maximum tolerated dose (40 µm). In female Balb/C mice, a single intraperitoneal dose (6 mg/kg) was rapidly absorbed with a maximum serum concentration of 3.4 ± 0.27 µm. Jadomycin B concentrations declined biphasically with an elimination half-life of 1.7 ± 0.058 h. In the 4T1 mouse mammary carcinoma model, jadomycin B (12 mg/kg every 12 h from day 6 to 15 after tumor cell injection) decreased primary tumor volume compared to vehicle control. Jadomycin B-treated mice did not exhibit weight loss, nor significant increases in biomarkers of impaired hepatic (alanine aminotransferase) and renal (creatinine) function. In conclusion, jadomycin B demonstrated a good safety profile and provided partial anti-tumoral effects, warranting further dose-escalation safety and efficacy studies in MDR breast cancer models.

Evaluation of the in vivo and in vitro anti-inflammatory activity of a new hybrid NSAID tetrahydropyran derivative.

Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(±)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro-2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-α, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.

Generation of prolactin-inducible protein (Pip) knockout mice by CRISPR/Cas9-mediated gene engineering.

Prolactin-inducible protein (PIP) is a multifunctional glycoprotein that is highly expressed and found in the secretions of apocrine glands such as salivary, lacrimal, and sweat glands including the mammary glands. PIP has been implicated in various diseases, including breast cancer, gross cystic disease of the breast, keratoconus of the eye, and the autoimmune Sjögren's syndrome. Here we have generated a Pip knockout (KO) mouse using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRSPR-associated (Cas)9 system. The Cas9 protein and two single guide RNAs targeting specific regions for both exons 1 and 2 of the Pip gene were microinjected into mouse embryos. The deletions and insertions promoted by CRISPR/Cas9 system on the Pip gene successfully disrupted Pip protein coding, as confirmed by PCR genotyping, sequencing, and ultimately Western blot analysis. This mouse model was generated in the inbred C57Bl/6J mouse, which exhibits lower genetic variation. This novel CRISPR Pip KO mouse model will not only be useful for future studies to interrogate the multifunctional role of PIP in physiological processes but will facilitate a broader understanding of the function of PIP in vivo while providing unprecedented insight into its role in a spectrum of diseases attributed to the deregulation of the PIP gene.

Isovitexin attenuates tumor growth in human colon cancer cells through the modulation of apoptosis and epithelial-mesenchymal transition via PI3K/Akt/mTOR signaling pathway.

Isovitexin, a biologically active flavone C-glycosylated derivative, has a variety of biological activities. We aimed to identify the effect of isovitexin (Isov) on colon cancer. Human colonic epithelial cells (HCECs) and cancer cells were treated with Isov and Cell Counting Kit-8 (CCK8) was used to detect cell proliferation and calculate the half-inhibitory concentration (IC50). The biological activity of cancer cells was assessed. The tumor size and volume were recorded. Protein expression levels were analyzed by western blotting. Isov inhibited cancer cell proliferation but had little cytotoxicity on HCECs. Isov significantly attenuated cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and induced cell apoptosis., This trend was blocked by insulin-like growth factor-1 (IGF-1) treatment. The expression levels of phosphorylated phosphatidylinositol 3-kinasep (p-PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and B cell lymphoma-2 (Bcl-2) decreased when treated with Isov, while the levels of Bcl2-associated X (Bax) and caspase-3 significantly increased. After Isov treatment, the tumor volume and weight were decreased, and the levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2 significantly decreased in tumor tissues. Our findings demonstrated that Isov inhibited cancer cell migration, invasion, and EMT. Isov may be a new potential treatment for colon cancer.

Voluntary running of defined distances alters bone microstructure in C57BL/6 mice fed a high-fat diet.

Obesity increases the risk for pathological conditions such as bone loss. On the other hand, physical exercise reduces body adiposity. To test the hypothesis that physical activity improves bone quality, we evaluated voluntary running of defined distances on trabecular and cortical microstructure in mice fed a high-fat diet (HFD). Sedentary mice were fed the standard AIN93G diet or the HFD. Mice fed the HFD remained sedentary or were assigned to unrestricted running or 75%, 50%, and 25% of unrestricted running with an average running activity at 8.3, 6.3, 4.2, and 2.1 km per day, respectively. The bone structural differences found in sedentary mice were that HFD, compared with the AIN93G diet, resulted in a lower bone volume fraction (BV/TV) and a higher structure model index (SMI) in vertebrae. Running had a greater effect on trabecular microstructure in femurs than in vertebrae; the decrease in SMI and an increase in trabecular thickness (Tb.Th) were in dose-dependent manners. Running was positively correlated with BV/TV and Tb.Th and inversely correlated with SMI in femurs. The HFD increased plasma concentrations of tartrate-resistant acid phosphatase 5b, a marker of bone resorption, in sedentary mice, while running decreased it in a dose-dependent manner. The findings show that voluntary running improves bone quality in young adult mice fed an HFD. Novelty: The high-fat diet alters bone microstructure by increasing bone resorption. Quantitative voluntary running improves bone microstructure through its attenuation of bone resorption in mice fed a high-fat diet.

Vascular and renal telomere shortening in mice exposed to chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is a chronic condition characterized by chronic intermittent hypoxia (IH) and is associated with cardiovascular (CVD) and chronic kidney diseases (CKD). Patients with OSA have increased biomarkers of aging such as telomere shortening. We used PCR to report shortened telomere lengths in aortic and renal tissues from mice exposed to 8 weeks of IH. Our data indicate that IH, a hallmark of OSA, accelerates vascular and renal aging that may contribute to OSA-induced CVD and CKD.

Managing the bacterial contamination risk in an axenic mice animal facility.

A gap exists between good laboratory practices with axenic animals and the procedures applied. This work examined the efficacy of sodium dichloroisocyanurate (MB-10) and potassium peroxymonosulfate (Virkon™) disinfectants, as well as the appropriate soaking time for materials used with the ISOcage Biosafety Station™. We also compared the microbial load in cage systems hosting mice over 2 weeks in axenic rooms (ARs) and in typical specific-pathogen-free (SPF) non-axenic rooms (NARs) to identify resistant microorganisms, targeted for longer soaking disinfection, and evaluated the necessary procedures for reducing the microbial load in AR. Staphylococcus was the most frequently isolated genus (in both ARs and NARs). An average of three spore-forming microorganisms per cage were counted from AR. The disinfection time to reach 1 log reduction for Bacillus atrophaeus spores varied from 138 s (100 ppm MB-10) to 290 (Virkon™) to <20 s for S. epidermidis (100 ppm MB-10). AR management protocols lead to a microbial load that is 1000 times lower than that found in NARs. Data comparing the microbial load in SPF and axenic facilities can be used to improve the effectiveness of their microbial control procedures.

Anti-atherogenic properties of Kgengwe (Citrullus lanatus) seed powder in low-density lipoprotein receptor knockout mice are mediated through beneficial alterations in inflammatory pathways.

Kgengwe fruits are commonly consumed in sub-Saharan countries. Recent reports indicated low coronary artery disease rates in those regions. To investigate anti-atherogenic properties and potential mechanisms of action of Kgengwe seed powder (KSP), male low-density lipoprotein receptor knockout (LDL-r-KO) mice were fed with an atherogenic diet supplemented with (treated, n = 10) or without (controls, n = 10) 10% (w/w) KSP for 20 weeks. Proximate analysis revealed that KSP contained 38% fibre and 15% lipids. KSP supplementation was not associated with significant changes in body weight gain rate, food intake, and plasma lipid levels. However, the average atherosclerotic lesion size in the aortic roots in the KSP-treated group was 58% smaller than that in the control group (0.26 vs 0.11 mm2, p < 0.05). This strong anti-atherogenic effect was associated with significant increases in the average plasma levels of certain cytokines such as IL-10 (6 vs 13 pg/mL, p < 0.05), GM-CSF (0.1 vs 0.2 pg/mL, p < 0.05), and EPO (7 vs 16 pg/mL, p < 0.05) along with reductions in the average levels of plasma MCP-1 (19 vs 14 pg/mL, p < 0.05) and MIP-2 (28 vs 13 pg/mL, p < 0.05). Except for relatively high levels of saturated fatty acids, KSP possesses balanced nutrient compositions with strong anti-atherogenic properties, which may be mediated through alterations in inflammatory pathways. Additional studies warrant confirmation and mechanism(s) of action of such effects. Novelty: Kgengwe seeds prevent atherogenesis in LDL-r-KO mice. Kgengwe seeds increase circulating levels of IL-10 and EPO. No reduction in plasma total cholesterol levels.

Characterization of primary adult mouse cardiac fibroblast cultures.

The role of cardiac fibroblasts (CFs) in disease states has been a focus of cardiovascular research over the past decade. Here, we briefly describe methods for isolation and characterization of CFs from adult mouse ventricles. Primary cultures were stained using antibodies for several marker proteins such as α-smooth muscle actin (αSMA), vimentin, and discoidin domain receptor 2 (DDR2) to confirm the identity of CFs or cardiac myofibroblasts (CMFs). Most cells in primary cultures consisted of CFs, with very low frequencies of endothelial cells, cardiomyocytes, and smooth muscle cells. We compared marker expression between cultures that were not passaged (P0) or passaged for few times (P1-3). When compared with P1-3 cultures, P0 cultures consistently displayed a lower percentage of cells positive for αSMA and DDR2, whereas vimentin expression was significantly higher in P0 cultures compared with P1-3 cultures. P0 cells were also smaller in area than P1-3 cells. Further, P1-3 mouse CFs were found to express both ß1 and ß2 adrenergic receptors (ARs) and ß1ARs were more readily detected on the cell surface compared with ß2ARs. In summary, mouse CF cultures underwent phenotype conversion into CMFs after passaging, consistent with what is seen with CF cultures from other species.

Receptor for advanced glycation end products modulates oxidative stress and mitochondrial function in the soleus muscle of mice fed a high-fat diet.

Accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) are implicated in the progression of pathologies associated with aging, chronic inflammation, diabetes, and cellular stress. RAGE activation is also implicated in cardiovascular complications of type 2 diabetes, such as nephropathy, retinopathy, accelerated vascular diseases, and cardiomyopathy. Studies investigating the effects of AGE/RAGE axis activation on skeletal muscle oxidative stress and metabolism are more limited. We tested whether a high-fat diet (HFD) would alter circulating AGE concentration, skeletal muscle AGE accumulation, and oxidative stress in wild-type and RAGE-deficient mice. The physiological significance of AGE/RAGE axis activation in HFD-fed mice was evaluated in terms of exercise tolerance and mitochondrial respiratory chain complex activity. HFD elicited adiposity, abnormal fat distribution, and oral glucose intolerance. HFD also induced accumulation of Nε-carboxymethyl-l-lysine, increased protein carbonyl levels, and impaired respiratory chain complex activity in soleus muscle. Ablation of RAGE had no effects on weight gain and oral glucose tolerance in HFD-fed mice. Peak aerobic capacity and mitochondrial cytochrome-c oxidase activity were restored in HFD-fed RAGE-/- mice. We concluded that RAGE signaling plays an important role in skeletal muscle homeostasis of mice under metabolic stress. Novelty HFD in mice induces accumulation of AGEs, oxidative stress, and mitochondrial dysfunction in the soleus muscle. RAGE, the multi-ligand receptor for AGEs, modulates oxidative stress and mitochondrial electron transport chain function in the soleus muscle of HFD-fed mice.

[A Mythological Anamnesis: from AIDS Spiders to the Bats of Ebola or Covid-19 - Revised Version of the Paper Presented at the Colloquium "Cultural and Social Perspectives on Epidemics", musée du quai Branly-Jacques-Chirac, June 27, 2019]. / Une anamnèse mythologique : des araignées du sida aux chauves-souris d'Ebola ou de la Covid-19 ­ Version remaniée de la communication présentée au colloque Regards culturels et sociaux autour des épidémies, musée du quai Branly-Jacques-Chirac le 27 juin 2019.

This article focuses on some representations of the origin of AIDS and Ebola in Burkina Faso, against a new background of Covid-19 which began in early 2020 in connection with two animals: the spider and the bat. These are also, if not first and foremost, heroes of oral literature (from tales to myths) from this region of West Africa. It is up to anthropologists to explore the meandering symbolism and imagination of these liminal animals that move back and forth between the worlds inhabited by humans and the "bush" worlds of non-humans. Here arises a mythological anamnesis. These "trickster" animals challenge categories and understanding of both virologists and anthropologists.

Cet article porte sur quelques représentations de l'origine du sida et d'Ebola en pays lobi burkinabè, avec la Covid-19 en nouvel arrière-plan depuis le début de l'année 2020, en lien avec deux animaux : l'araignée et la chauve-souris. Ce sont aussi, voire d'abord, des héros de la littérature orale (des contes aux mythes) de cette région d'Afrique de l'Ouest. Des anthropologues ont exploré les méandres des symboliques et des imaginaires de ces animaux liminaires qui vont et viennent entre les mondes habités par les humains et les univers de « brousse ¼ des non-humains. Une anamnèse mythologique est mise à jour. Ces animaux rusés se jouent de nos catégories et de notre entendement, virologues et anthropologues ici confondus.

N-acetyl-seryl-aspartyl-lysyl-proline treatment protects heart against excessive myocardial injury and heart failure in mice.

Myocardial infarction (MI) in mice results in cardiac rupture at 4-7 days after MI, whereas cardiac fibrosis and dysfunction occur later. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory, anti-fibrotic, and pro-angiogenic properties. We hypothesized that Ac-SDKP reduces cardiac rupture and adverse cardiac remodeling, and improves function by promoting angiogenesis and inhibiting detrimental reactive fibrosis and inflammation after MI. C57BL/6J mice were subjected to MI and treated with Ac-SDKP (1.6 mg/kg per day) for 1 or 5 weeks. We analyzed (1) intercellular adhesion molecule-1 (ICAM-1) expression; (2) inflammatory cell infiltration and angiogenesis; (3) gelatinolytic activity; (4) incidence of cardiac rupture; (5) p53, the endoplasmic reticulum stress marker CCAAT/enhancer binding protein homology protein (CHOP), and cardiomyocyte apoptosis; (6) sarcoplasmic reticulum Ca2+ ATPase (SERCA2) expression; (7) interstitial collagen fraction and capillary density; and (8) cardiac remodeling and function. Acutely, Ac-SDKP reduced cardiac rupture, decreased ICAM-1 expression and the number of infiltrating macrophages, decreased gelatinolytic activity, p53 expression, and myocyte apoptosis, but increased capillary density in the infarction border. Chronically, Ac-SDKP improved cardiac structures and function, reduced CHOP expression and interstitial collagen fraction, and preserved myocardium SERCA2 expression. Thus, Ac-SDKP decreased cardiac rupture, ameliorated adverse cardiac remodeling, and improved cardiac function after MI, likely through preserved SERCA2 expression and inhibition of endoplasmic reticulum stress.

Anti-adipogenesis and antioxidative defense status of a crude extract of 'Kalasin 2' peanut sprouts in 3T3-L1 mouse adipocytes.

The aim of this study was to investigate the effects of extracts from germinated (GPE) and non-germinated peanuts (NGPE) on adipogenesis and oxidative status in normal and oxidative-stress-induced 3T3-L1 mouse adipocytes. The treated cells were analysed for cell growth, lipid accumulation, levels of intracellular reactive oxygen species (ROS), and the expression levels of mRNAs and proteins related to adipogenesis and antioxidative defense systems. The results indicated that an extract from peanuts made 9 days after germination (9GPE) reduced lipid contents and mRNA expression of adipogenesis-related genes to a greater extent than an extract from peanuts made 1-day after germination (1GPE) or from NGPE, respectively. In oxidative-stress-induced adipocytes, 9GPE decreased ROS levels, lipid content, and the protein expression of peroxisome-proliferator-activated receptor gamma, and also increased the protein expression of antioxidants. These results illustrate the anti-adipogenic capacity and oxidative status improvement achievable with GPE, and that it could be used as a putative therapeutic agent in the prevention of and (or) treatment of obesity and diseases associated with oxidative stress.

Olive oil promotes wound healing of mice pressure injuries through NOS-2 and Nrf2.

The pressure injury environment is characterized by overproduction of reactive oxygen species and exacerbated inflammation, which impair the healing of these lesions. Mediterranean-like diet may be a good intervention to improve the healing of pressure injury owing to its anti-inflammatory and antioxidant components. Thus, this study evaluated the hypothesis that olive oil, as a main source of lipid in Mediterranean diet, could improve cutaneous wound healing of pressure injury in mice. Male Swiss mice were randomly divided into standard, olive oil, or soybean oil plus olive oil groups and fat represented 10% of total calories in all groups. Four weeks after the beginning of diet administration, 2 cycles of ischemia-reperfusion (IR) by external application of 2 magnets disks were performed in the dorsal skin to induce pressure injury formation. Fourteen days after the end of the second IR cycle, olive oil-based diet reduced neutrophils cells and cyclooxygenase-2 protein expression and increased nitric oxide synthase-2 and protein and lipid oxidation. Olive oil based-diet also increased nuclear factor erythroid 2-related factor 2 protein expression and collagen type I precursor protein expression. In addition, administration of olive oil-based diet promoted wound closure at 7, 10, and 14 days after the end of the second IR cycle. These findings support the hypothesis that olive oil-based diet improves cutaneous wound healing of pressure injury in mice through the reduction of inflammation and stimulation of redox equilibrium.

Evaluating the efficacy of sample collection approaches and DNA metabarcoding for identifying the diversity of plants utilized by nectivorous bats.

In this study, we evaluated the efficacy of sample collection approaches and DNA metabarcoding to identify plants utilized by nectivorous bats. Samples included guano collected from beneath bat roosts and pollen-swabs from bat fur, both of which were subjected to DNA metabarcoding and visual identification of pollen (microscopy) to measure plant diversity. Our objectives were to determine whether DNA metabarcoding could detect likely food plants of nectivorous bats, whether sample types would produce different estimates of plant diversity, and to compare results of DNA metabarcoding to visual identification. Visual identification found that 99% of pollen was from Agave, which is thought to be the bats' main food source. The dominant taxon found by metabarcoding was also Agavoideae, but a broader diversity of plant species was also detected, many of which are likely "by-catch" from the broader environment. Metabarcoding outcomes differed between sample types, likely because pollen-swabs measured the plant species visited by bats and guano samples measured all items consumed in the bat's diet, even those that were not pollen or nectar. Overall, metabarcoding is a powerful, high-throughput tool to understand bat ecology and species interactions, but careful analysis of results is necessary to derive accurate ecological conclusions.

Two indole-2-carboxamide derivatives attenuate lipopolysaccharide-induced acute lung injury by inhibiting inflammatory response.

Acute lung injury (ALI) is the leading cause of mortality in the intensive care unit. Currently, there is no effective pharmacological treatment for ALI. In our previous study, we reported that Lg25 and Lg26, two indole-2-carboxamide derivatives, inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokines in vitro and attenuated LPS-induced sepsis in vivo. In the present study, we confirmed data from previous studies that LPS significantly induced pulmonary edema and pathological changes in lung tissue, increased protein concentration and number of inflammatory cells in bronchoalveolar lavage fluids (BALF), and increased inflammatory cytokine TNF-α expression in serum and BALF, pro-inflammatory genes expression, and macrophages infiltration in lung tissue. However, pretreatment with Lg25 and Lg26 significantly attenuated the LPS-induced changes in mice. Taken together, these data indicate that the newly discovered indole-2-carboxamide derivatives could be particularly useful in the treatment of inflammatory diseases such as ALI.

Therapeutic administration of enrofloxacin in mice does not select for fluoroquinolone resistance in Campylobacter jejuni.

Enrofloxacin is registered for therapeutic use in beef cattle to treat bovine respiratory disease in Canada. A murine model was used to experimentally examine the impact of therapeutic administration of enrofloxacin on fluoroquinolone resistance development in Campylobacter jejuni. Administration of enrofloxacin to mice via subcutaneous injection or per os routes resulted in equivalent levels of bioactive enrofloxacin within the intestine, but bioactivity was short-lived (<48 h after cessation). Enrofloxacin administration did not affect densities of total bacteria, Firmicutes, or Bacteroidetes in digesta and had modest impacts on densities of Enterobacteriaceae. All mice inoculated with C. jejuni NCTC 11168 became persistently colonized by the bacterium. Enrofloxacin reduced C. jejuni cell densities within the cecal and colonic digesta for all treatments, and densities shed in feces as a function of antibiotic duration. None of the C. jejuni isolates recovered from mice after administration of enrofloxacin (n = 260) developed resistance to ciprofloxacin regardless of method or duration of administration. Furthermore, only modest shifts in the minimum inhibitory concentration of the isolates by treatment were noted. The study findings indicate that the risk posed by short-term subcutaneous administration of enrofloxacin for the development of fluoroquinolone resistance in mammals is low.