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Background: D-limonene (D-L) is the major monocyclic monoterpene in citrus plants with anti-inflammatory properties. Pulmonary hypertension (PH) can cause right heart dysfunction and increases the risk of death, partially due to inflammatory response in the heart., Objective: To evaluate the possible protective effect of D-L on cardiac function in a rat model of monocrotaline-induced PH (MCT-PH)., Methods: Electrocardiogram was monitored in vivo. Masson Trichrome technique was deployed to verify fibrosis in the heart. Contractility function of isolated atrial tissue was studied using organ bath chamber. Real-time quantitative PCR was applied to quantify inflammation in the right ventricle., Results: The MCT-PH group showed electrical and structural heart remodeling, with the presence of fibrosis in the cardiac tissue and in vivo electrocardiographic changes. Treatment with D-L partially prevented the development of tissue fibrosis and the increase in P wave duration in the MCT-PH group. The contraction and relaxation velocity of isolated right and left atrium were accelerated in CTR and MCT-PH animals treated with D-L. Finally, D-L was able to prevent the abnormal expression of the key inflammatory cytokines (interleukin 1-β, interleukin 6 and tumor necrosis factor-α) in the right ventricle of MCT-PH animals. D-L was able to enhance the production of the anti-inflammatory cytokine Interleukin-10., Conclusion: Our results showed that in vivo administration of D-L partially prevented the molecular, structural and functional remodeling of the heart in the MCT-PH model with attenuation of the inflammatory response in the heart.

Tebuconazole (TEB), a widely used pesticide in agriculture to combat fungal infections, is commonly detected in global food, potable water, groundwater, and human urine samples. Despite its known in vivo toxicity, its impact on heart function remains unclear. In a 28-day study on male Wistar rats (approximately 100 g), administering 10 mg/kg/day TEB or a vehicle (control) revealed no effect on body weight gain or heart weight, but an increase in the infarct area in TEB-treated animals. Notably, TEB induced time-dependent changes in in vivo electrocardiograms, particularly prolonging the QT interval after 28 days of administration. Isolated left ventricular cardiomyocytes exposed to TEB exhibited lengthened action potentials and reduced transient outward potassium current. TEB also increased reactive oxygen species (ROS) production in these cardiomyocytes, a phenomenon reversed by N-acetylcysteine (NAC). Furthermore, TEB-treated animals, when subjected to an in vivo dobutamine (Dob) and caffeine (Caf) challenge, displayed heightened susceptibility to severe arrhythmias, a phenotype prevented by NAC. In conclusion, TEB at the no observed adverse effect level (NOAEL) dose adversely affects heart electrical function, increases arrhythmic susceptibility, partially through ROS overproduction, and this phenotype is reversible by scavenging ROS with NAC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The high incidence of atrial arrhythmias in pulmonary hypertension (PH) might be associated with poor prognosis, and the left atrium (LA) may play a role in this. An important finding in PH studies is that LA remodeling is underestimated., Objective: This study investigated LA morphology and mechanical function, as well as the susceptibility to develop arrhythmias in a monocrotaline-induced PH (MCT-PH) model., Methods: Wistar rats aged 4 weeks received 50 mg/kg of MCT. Electrocardiography and histology analysis were performed to evaluate the establishment of the MCT-PH model. The tissue was mounted in an isolated organ bath to characterize the LA mechanical function., Results: Compared with the control group (CTRL), the MCT-PH model presented LA hypertrophy and changes in cardiac electrical activity, as evidenced by increased P wave duration, PR and QT interval in MCT-PH rats. In LA isolated from MCT-PH rats, no alteration in inotropism was observed; however, the time to peak contraction was delayed in the experimental MCT-PH group. Finally, there was no difference in arrhythmia susceptibility of LA from MCT-PH animals after the burst pacing protocol., Conclusion: The morphofunctional remodeling of the LA did not lead to increased susceptibility to ex vivo arrhythmia after application of the burst pacing protocol.

Pathogenic spirochetes from genus Leptospira are etiologic agents of leptospirosis. Cellular vaccines against Leptospira infection often elicit mainly response against the LPS antigen of the serovars present in the formulation. There is no suitable protein candidate capable of replacing whole-cell vaccines, thus requiring new approaches on vaccine development to improve leptospirosis prevention. Our goal was to develop a whole-cell vaccine sorovar-independent based on LPS removal and conservation of protein antigens exposure, to evaluate the protective capacity of monovalent or bivalent vaccines against homologous and heterologous virulent Leptospira in hamster. Leptospire were subjected to heat inactivation, or to LPS extraction with butanol and in some cases further inactivation with formaldehyde. Hamsters were immunized and challenged with homologous or heterologous virulent serovars, blood and organs were collected from the survivors for bacterial quantification, chemokine evaluation, and analysis of sera antibody reactivity and cross-reactivity by Western blot. Immunization with either heated or low LPS vaccines with serovar Copenhageni or Canicola resulted in 100% protection of the animals challenged with homologous virulent bacteria. Notably, different from the whole-cell vaccine, the low LPS vaccines produced with serovar Canicola provided only partial protection in heterologous challenge with the virulent Copenhageni serovar. Immunization with bivalent formulation results in 100% protection of immunized animals challenged with virulent serovar Canicola. All vaccines produced were able to eliminate bacteria from the kidney of challenged animals. All the vaccines raised antibodies capable to recognize antigens of serovars not present in the vaccine formulation. Transcripts of IFNγ, CXCL16, CCL5, CXCL10, CXCR6, and CCR5, increased in all immunized animals. Conclusion: Our results showed that bivalent vaccines with reduced LPS may be an interesting strategy for protection against heterologous virulent serovars. Besides the desirable multivalent protection, the low LPS vaccines are specially promising due to the expected lower reatogenicity., Competing Interests: The author(s) declare(s) that they have no competing interests.

Background: Leptospirosis is a widespread zoonosis caused by pathogenic prokaryotic microbes of the genus Leptospira. Although there are several reports in the literature, host-pathogen interaction is still poorly understood. The role of chemokine expression is important on the chemotaxis, activation and regulation of immune cells. Recent studies have shown that their expression profiles play an important role on the severity of leptospirosis outcome. We evaluated the phagocytosis of Leptospira by spleens cells from C3H/HeJ, C3H/HePas and BALB/c mouse strains, respectively susceptible, intermediate and resistant to leptospirosis, and by RAW 264.7 macrophages. Besides, we evaluated the effects of CCL2 treatment on the phagocytosis. The cells were incubated with or without CCL2 chemokine, and infected with virulent L. interrogans sv Copenhageni. Cells and culture supernatants were collected for subsequent analysis., Results: The number of leptospires was higher in BALB/c cells, CCL2 pre-treated or only infected groups, when compared to C3H/HeJ and C3H/HePas cells. Indeed, CCL2 activation did not interfere in the phagocytosis of Leptospira. Expression of chemokines CXCL5 and CCL8 levels were significantly inhibited in infected BALB/c cells when compared to the non-infected control., Conclusions: Higher ability to phagocytosis and early modulation of some chemokines correlated with the resistance to leptospirosis disease. Exposure to CCL2 did not interfere on phagocytosis of Leptospira in our experimental conditions, but acted in the modulation of chemokines expression during Leptospira infection.

The response of plants to grazing includes the production of chemical defense compounds such as proteases inhibitors and secondary metabolites as flavonoids, which makes them less palatable to feeding and negatively affecting the physiology of insects. The aim of this study was to evaluate the phytochemical response of soybean cultivars (Glycine max (L.) Merrill) resistant (IAC-17, IAC-24) and susceptible (IAC-P1) to insects after mechanical damage. These cultivars were mechanically injured, and after 24 hours samples of these plants were analyzed by HPLC to identify and quantify flavonoids. The flavonoids daidzein, quercetin, and rutin were quantified, with the highest concentration of daidzin in soybean cultivars after mechanical damage. Rutin was biosynthesized by IAC-24. The cultivars IAC-PL1, IAC-17, and IAC-24 did not show a flavonoid response to mechanical damage. The soybean cultivars are not dependent on mechanical damage to produce flavonoids.