Mitigating Age-Related Ovarian Dysfunction with the Anti-Inflammatory Agent MIT-001.

Ovarian aging is a major obstacle in assisted reproductive medicine because it leads to ovarian dysfunction in women of advanced age. Currently, there are no effective treatments to cure age-related ovarian dysfunction. In this study, we investigated the effect of MIT-001 on the function of aged ovaries. Young and old mice were utilized in this study. MIT-001 was intraperitoneally administered, and the number of follicles and oocytes was analyzed. Each group was then retrieved for RNA and protein isolation. Total RNA was subjected to mRNA next-generation sequencing. Protein extracts from ovarian lysates were used to evaluate various cytokine levels in the ovaries. MIT-001 enhanced follicles and the number of oocytes were compared with non-treated old mice. MIT-001 downregulated immune response-related transcripts and cytokines in the ovaries of old mice. MIT-001 modulates the immune complex responsible for generating inflammatory signals and has the potential to restore the function of old ovaries and improve female fertility.

Dynamic Change of R-Loop Implicates in the Regulation of Zygotic Genome Activation in Mouse.

In mice, zygotic genome activation (ZGA) occurs in two steps: minor ZGA at the one-cell stage and major ZGA at the two-cell stage. Regarding the regulation of gene transcription, minor ZGA is known to have unique features, including a transcriptionally permissive state of chromatin and insufficient splicing processes. The molecular characteristics may originate from extremely open chromatin states in the one-cell stage zygotes, yet the precise underlying mechanism has not been well studied. Recently, the R-loop, a triple-stranded nucleic acid structure of the DNA/RNA hybrid, has been implicated in gene transcription and DNA replication. Therefore, in the present study, we examined the changes in R-loop dynamics during mouse zygotic development, and its roles in zygotic transcription or DNA replication. Our analysis revealed that R-loops persist in the genome of metaphase II oocytes and preimplantation embryos from the zygote to the blastocyst stage. In particular, zygotic R-loop levels dynamically change as development proceeds, showing that R-loop levels decrease as pronucleus maturation occurs. Mechanistically, R-loop dynamics are likely linked to ZGA, as inhibition of either DNA replication or transcription at the time of minor ZGA decreases R-loop levels in the pronuclei of zygotes. However, the induction of DNA damage by treatment with anticancer agents, including cisplatin or doxorubicin, does not elicit genome-wide changes in zygotic R-loop levels. Therefore, our study suggests that R-loop formation is mechanistically associated with the regulation of mouse ZGA, especially minor ZGA, by modulating gene transcription and DNA replication.

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer.

Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.

Mitochondrial Peptide Humanin Protects Silver Nanoparticles-Induced Neurotoxicity in Human Neuroblastoma Cancer Cells (SH-SY5Y).

The extensive usage of silver nanoparticles (AgNPs) as medical products such as antimicrobial and anticancer agents has raised concerns about their harmful effects on human beings. AgNPs can potentially induce oxidative stress and apoptosis in cells. However, humanin (HN) is a small secreted peptide that has cytoprotective and neuroprotective cellular effects. The aim of this study was to assess the harmful effects of AgNPs on human neuroblastoma SH-SY5Y cells and also to investigate the protective effect of HN from AgNPs-induced cell death, mitochondrial dysfunctions, DNA damage, and apoptosis. AgNPs were prepared with an average size of 18 nm diameter to study their interaction with SH-SY5Y cells. AgNPs caused a dose-dependent decrease of cell viability and proliferation, induced loss of plasma-membrane integrity, oxidative stress, loss of mitochondrial membrane potential (MMP), and loss of ATP content, amongst other effects. Pretreatment or co-treatment of HN with AgNPs protected cells from several of these AgNPs induced adverse effects. Thus, this study demonstrated for the first time that HN protected neuroblastoma cells against AgNPs-induced neurotoxicity. The mechanisms of the HN-mediated protective effect on neuroblastoma cells may provide further insights for the development of novel therapeutic agents against neurodegenerative diseases.

Differential Immunomodulatory Effect of Graphene Oxide and Vanillin-Functionalized Graphene Oxide Nanoparticles in Human Acute Monocytic Leukemia Cell Line (THP-1).

Graphene and its derivatives are emerging as attractive materials for biomedical applications, including antibacterial, gene delivery, contrast imaging, and anticancer therapy applications. It is of fundamental importance to study the cytotoxicity and biocompatibility of these materials as well as how they interact with the immune system. The present study was conducted to assess the immunotoxicity of graphene oxide (GO) and vanillin-functionalized GO (V-rGO) on THP-1 cells, a human acute monocytic leukemia cell line. The synthesized GO and V-rGO were characterized by using various analytical techniques. Various concentrations of GO and V-rGO showed toxic effects on THP-1 cells such as the loss of cell viability and proliferation in a dose-dependent manner. Cytotoxicity was further demonstrated as an increased level of lactate dehydrogenase (LDH), loss of mitochondrial membrane potential (MMP), decreased level of ATP content, and cell death. Increased levels of reactive oxygen species (ROS) and lipid peroxidation caused redox imbalance in THP-1 cells, leading to increased levels of malondialdehyde (MDA) and decreased levels of anti-oxidants such as glutathione (GSH), glutathione peroxidase (GPX), super oxide dismutase (SOD), and catalase (CAT). Increased generation of ROS and reduced MMP with simultaneous increases in the expression of pro-apoptotic genes and downregulation of anti-apoptotic genes suggest that the mitochondria-mediated pathway is involved in GO and V-rGO-induced apoptosis. Apoptosis was induced consistently with the significant DNA damage caused by increased levels of 8-oxo-dG and upregulation of various key DNA-regulating genes in THP-1 cells, indicating that GO and V-rGO induce cell death through oxidative stress. As a result of these events, GO and V-rGO stimulated the secretion of various cytokines and chemokines, indicating that the graphene materials induced potent inflammatory responses to THP-1 cells. The harshness of V-rGO in all assays tested occurred because of better charge transfer, various carbon to oxygen ratios, and chemical compositions in the rGO. Overall, these findings suggest that it is essential to better understand the parameters governing GO and functionalized GO in immunotoxicity and inflammation. Rational design of safe GO-based formulations for various applications, including nanomedicine, may result in the development of risk management methods for people exposed to graphene and graphene family materials, as these nanoparticles can be used as delivery agents in various biomedical applications.

Clinical response to isotretinoin and interferon-α of two dogs with cutaneous epitheliotropic T-cell lymphoma: a case report.

BACKGROUND: There is no specific therapy for cutaneous epitheliotropic T-cell lymphoma (CETL). The administration of retinoids in conjunction with interferon-α (IFN-α) in CETL has not been reported in dogs. CASE PRESENTATION: Two dogs (Shih tzu and Miniature pinscher) presented with multiple nodular skin lesions. Histopathological examination revealed diffuse infiltrations of lymphocytes in the epidermis and dermis, with a CD3-positive immunophenotypic profile. Based on the clinical and histopathological examination, CETL was diagnosed. Both dogs were treated with isotretinoin in combination with IFN-α and showed clinical improvement with complete or partial remission. The disease in these dogs was well-controlled for more than 264 days of overall median survival time without any additional clinical signs after initiation of the treatment. In both the cases, the dogs were followed up for 27 months, and 10 months without any evidence of recurrence or metastasis, respectively. CONCLUSIONS: We describe the clinical efficacy of isotretinoin combined with IFN-α in 2 dogs with CETL. Long-term management with isotretinoin combined with IFN-α was effective in treating CETL in these cases.

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer.

Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significantrole in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Someof the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeuticwindow and undesired side effects of available anticancer drugs and the limitations of anticancerdrugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranosticcarriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallicnanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation andleads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatictumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapiesin various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies.Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is lessthan that of the combination of NPs and anticancer drugs. Combination therapy has long beenadopted as the standard first-line treatment of several malignancies to improve the clinical outcome.Combination therapy with anticancer drugs has been shown to generally induce synergistic drugactions and deter the onset of drug resistance. Therefore, this review is designed to report andanalyze the recent progress made to address combination therapy using NPs and anticancer drugs.We first provide a comprehensive overview of the angiogenesis and of the different types of NPscurrently used in treatments of cancer; those emphasized in this review are liposomes, polymericNPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbonnanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used forcombination therapy with various anticancer agents. Nanotechnology has provided the convenienttools for combination therapy. However, for clinical translation, we need continued improvementsin the field of nanotechnology.

Combination Effect of Silver Nanoparticles and Histone Deacetylases Inhibitor in Human Alveolar Basal Epithelial Cells.

Although many treatment strategies have been reported for lung disease, the mechanism of combination therapy using silver nanoparticles (AgNPs) and histone deacetylases inhibitors (HDACi) remains unclear. Therefore, innovative treatment strategies are essential for addressing the therapeutic challenges of this highly aggressive lung cancer. AgNPs and HDACi seem to be the best candidates for anticancer therapy because of their anti-proliferative effect in a variety of cancer cells. First, we synthesized AgNPs using wogonin as a reducing and stabilizing agent, following which the synthesized AgNPs were characterized by various analytical techniques. The synthesized AgNPs exhibited dose- and size-dependent toxicity towards A549 cells. Interestingly, the combination of AgNPs and MS-275 significantly induces apoptosis, which was accompanied by an increased level of reactive oxygen species (ROS); leakage of lactate dehydrogenase (LDH); secretion of TNFα; dysfunction of mitochondria; accumulation autophagosomes; caspase 9/3 activation; up and down regulation of pro-apoptotic genes and anti-apoptotic genes, respectively; and eventually, induced DNA-fragmentation. Our findings suggest that AgNPs and MS-275 induce cell death in A549 lung cells via the mitochondrial-mediated intrinsic apoptotic pathway. Finally, our data show that the combination of AgNPs and MS-275 is a promising new approach for the treatment of lung cancer and our findings contribute to understanding the potential roles of AgNPs and MS-275 in pulmonary disease. However, further study is warranted to potentiate the use of this combination therapy in cancer therapy trials.

Identification and characterization of putative stem cells in the adult pig ovary.

Recently, the concept of 'neo-oogenesis' has received increasing attention, since it was shown that adult mammals have a renewable source of eggs. The purpose of this study was to elucidate the origin of these eggs and to confirm whether neo-oogenesis continues throughout life in the ovaries of the adult mammal. Adult female pigs were utilized to isolate, identify and characterize, including their proliferation and differentiation capabilities, putative stem cells (PSCs) from the ovary. PSCs were found to comprise a heterogeneous population based on c-kit expression and cell size, and also express stem and germ cell markers. Analysis of PSC molecular progression during establishment showed that these cells undergo cytoplasmic-to-nuclear translocation of Oct4 in a manner reminiscent of gonadal primordial germ cells (PGCs). Hence, cells with the characteristics of early PGCs are present or are generated in the adult pig ovary. Furthermore, the in vitro establishment of porcine PSCs required the presence of ovarian cell-derived extracellular regulatory factors, which are also likely to direct stem cell niche interactions in vivo. In conclusion, the present work supports a crucial role for c-kit and kit ligand/stem cell factor in stimulating the growth, proliferation and nuclear reprogramming of porcine PSCs, and further suggests that porcine PSCs might be the culture equivalent of early PGCs.

Psychological Aspects of Glaucoma.

Glaucoma is a group of optic neuropathies that is more prevalent among the elderly population and commonly associates with comorbidities, including mental disorders in that population. This article reviews the relationship between glaucoma and mental disorders. In it, we discuss the coexistence of glaucoma and mental illnesses, including Alzheimer's disease, depression, and personality disorder. We also focus on the proper treatment approaches for glaucoma patients with mental comorbidity and poor treatment adherence. We summarize some cautiously recommended psychotherapeutic medications, while also discussing the psychologically adverse effects of antiglaucoma medications.

Anthracycline-induced cardiomyopathy in a dog treated with epirubicin.

An 8-year-old American cocker spaniel dog was diagnosed with dilated cardiomyopathy. Four years earlier, the dog had been diagnosed with multicentric lymphoma and had received 4 cycles of multi-agent chemotherapy, including doxorubicin and epirubicin. The total cumulative dose of epirubicin was 168 mg/m(2). Dilated cardiomyopathy was considered a consequence of epirubicin toxicity.

Cardiomyopathie induite par l'anthracycline chez un chien traité à l'épirubicine. Un chien Épagneul cocker américain a été diagnostiqué avec une cardiomyopathie dilatée. Quatre années plus tôt, le chien avait été diagnostiqué avec un lymphome multicentrique et avait reçu 4 cycles de chimiothérapie multi-agents, y compris la doxorubicine et l'épirubicine. La dose cumulative totale d'épirubicine était de 168 mg/m2. La cardiomyopathie dilatée est considérée comme une conséquence de la toxicité de l'épirubicine.(Traduit par Isabelle Vallières).

Uveodermatologic syndrome concurrent with keratoconjunctivitis sicca in a miniature poodle dog.

A 5-year-old, intact female miniature poodle dog was presented with chronic ophthalmic problems, facial poliosis, nasal depigmentation and multiple areas of alopecia over the trunk. Bilateral uveitis preceded dermatologic signs by 5 months and gradually worsened. The dog was diagnosed as having uveodermatologic syndrome (UDS) concurrent with keratoconjunctivitis sicca (KCS). Treatment with immunosuppressive drugs resolved the dermatologic lesions, but uveitis continued to progress.

Syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche chez un caniche miniature. Une chienne caniche miniature intacte âgée de 5 ans a été présentée avec des problèmes ophtalmiques chroniques, une poliose faciale, une dépigmentation nasale et plusieurs plaques d'alopécie sur le tronc. L'uvéite bilatérale a précédé les signes dermatologiques 5 mois auparavant et elle s'est graduellement aggravée. La chienne a été diagnostiquée comme atteinte du syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche. Le traitement avec des immunodépresseurs a résolu les lésions dermatologiques, mais l'uvéite a continué de progresser.(Traduit par Isabelle Vallières).

Staphylococcus pseudintermedius infection associated with nodular skin lesions and systemic inflammatory response syndrome in a dog.

A 10-year-old Pekingese dog with atopic dermatitis was referred due to pyrexia, multiple skin nodules, anorexia, and depression. The dog was diagnosed as having systemic inflammatory response syndrome (SIRS) induced by bacterial dermatitis. This case presents diagnosis and treatment of SIRS with staphylococcal skin infection in a dog that was immunosuppressed due to long-term use of corticosteroid.

Infection parStaphylococcus pseudintermediusassociée à des lésions cutanées nodulaires et à un syndrome de réaction inflammatoire systémique chez un chien. Un chien Pékinois âgé de 10 ans atteint de dermatite atopique a été référé en raison d'une pyrexie, de nodules cutanés multiples, d'anorexie et de dépression. Le chien a été diagnostiqué comme ayant un syndrome de réaction inflammatoire systémique (SRIS) induit par une dermatite bactérienne. Ce cas présente le diagnostic et le traitement du SRIS avec une infection aux staphylocoques cutanés chez un chien ayant une immunodépression causée par l'utilisation à long terme de corticostéroïdes.(Traduit par Isabelle Vallières).

Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals.

Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern.

Résistance aux fluoroquinolones et à la méthicilline dans les isolats oculaires deStaphylococcus pseudintermediusdes animaux de compagnie. La résistance aux fluoroquinolones et à la méthicilline a été déterminée pour 49 isolats oculaires de Staphylococcus pseudintermedius provenant de chiens atteints et exempts d'une maladie ophtalmique. La résistance a été observée pour la ciprofloxacine (40,8 %), l'ofloxacine (38,8 %), l'enrofloxacine (38,8 %), la levofloxacine (34,7 %) et la moxifloxacine (4,1 %). Dix-huit isolats, dont 16 étaient résistants à l'oxacilline, étaient positifs pour mecA. Neuf des 16 isolats de S. pseudintermedius positifs pour mecA résistants à l'oxacilline et étaient résistants à plus d'une fluoroquinolone et 2 isolats étaient résistants à 5 fluoroquinolones. La fréquence de l'occurrence du gène mecA et de la résistance aux fluoroquinolones était deux fois supérieure pour les isolats S. pseudintermedius dérivés de chiens atteints d'une maladie ophtalmique comparativement aux chiens sans maladie ophtalmique. La prévalence élevée de la résistance à la méthicilline et à la fluoroquinolone pour S. pseudintermedius chez les chiens atteints d'une maladie ophtalmique est préoccupante.(Traduit par Isabelle Vallières).

Case report: Small bowel obstruction secondary to congenital transmesenteric internal hernia in a cat.

An 8-month-old castrated male British Shorthair cat presented with acute anorexia and vomiting. The overall clinical presentation included generalized depression. Physical examination revealed palpable abdominal mass, thus foreign body or intussusception was suspected. Abdominal radiographs showed segmental dilation of small intestine and ultrasonography revealed target lesion with dilated small bowel loops and disrupted normal wall layering, suggestive of intussusception. Exploratory laparotomy confirmed congenital mesenteric defects associated with small intestinal obstruction. Surgical intervention involved dissection, ligation of encircling blood vessels, and closure of mesenteric defects. The cat was discharged after 3 days, exhibiting normal postoperative recovery. To our knowledge, this is the first case report of congenital mesenteric defect associated with small intestinal obstruction in a cat. While internal hernias are rare, it is essential to include them in the differential diagnosis for cases of intestinal obstruction, particularly in patients with no history of previous surgery or trauma. The potential for strangulation and ischemia in the affected loops elevates internal hernias to a critical, life-threatening condition, emphasizing the need for prompt recognition and urgent surgical intervention as an emergency.

Evaluation of autologous blood clot subsegmental pulmonary thromboembolism in minimally invasive experimental canine model.

The incidence and significance of subsegmental pulmonary (SSP) thromboembolism is currently under investigation. We aimed to evaluate the clinical and diagnostic features of SSP thromboembolism in an experimental canine model. Obstruction of pulmonary arterial branches was induced in three beagle dogs by intravenous injection of a barium-coated autologous blood clot (size, approximately 1.7 × 5 mm). The clinical signs, haemodynamic changes (blood pressure, electrocardiogram, echocardiography), coagulation (aPTT, PT, FDPs and D-dimer test) and cytokine variations (TNF-a, IL-4, IL-6, and IL-10) were evaluated over a 24-hour period. Multidetector computed tomography (MDCT) with contrast was conducted to evaluate the pulmonary obstruction, and histopathological confirmation was performed. Pulmonary artery pressure gradient (PAPG) was increased 12 h after the autologous blood clot injection (14.2 ± 2.8 mmHg to 23.6 ± 1.7 mmHg, P = 0.003) and normalized 24 h later (P < 0.01). Infused radiopaque clots were confirmed with MDCT and histopathological examination. Pulmonary parenchymal changes such as arterial dilation and inflammatory reactions were also confirmed in histopathological examinations and were barely observable in MDCT. Usually small emboli are not easily detected through CT imaging, and the clinical relevance of these emboli is controversial. In this experimental study, we made radiopaque small emboli and induced SSP thromboembolism. Thus, we infer that obstruction of the small segmental and subsegmental pulmonary arteries does result in a pulmonary thromboembolism (PTE) and PTE-related pulmonary parenchymal changes which could be clinically significant.

Mitochondria in reproduction.

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.

Case report: A novel occurrence of persistent left cranial vena cava coexisting with polycystic kidney disease in a cat.

A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease. Tachycardia with a systolic murmur (grade III/VI) was auscultated and for further diagnosis, echocardiography was performed. Based on echocardiography, persistent left cranial vena cava (PLCVC) was suspected due to enlargement of the coronary sinus and confirmed by saline contrast echocardiography. The dilated coronary sinus compressed the left atrium, and left ventricular hypertrophy with the systolic anterior motion of the mitral valve, aortic regurgitation, and mitral regurgitation were identified. After medical management using atenolol, left atrial function and other hemodynamics of the heart were improved, including the disappearance of regurgitation and normalization of left ventricular wall thickness. This case report describes the echocardiographic characteristics, diagnostic procedures, and disease progression in a cat with PLCVC after medical management using atenolol. Additionally, this is the first report of a cat with PLCVC, coexisting with polycystic kidney disease.

Case report: Villaret's syndrome caused by middle ear adenocarcinoma in a cat.

A 7-year-old castrated male American Shorthair cat presented with left-side Horner's syndrome and voice change. The overall clinical presentation included dysphagia, intermittent coughing, unilateral miosis, and third eyelid protrusion of the left eye. A topical 1% phenylephrine was applied, and miosis and protrusion of the third eyelid disappeared within 20 min which suggested a post-ganglionic lesion. Laryngoscopy showed left-sided laryngeal paralysis. Computed tomography (CT) identified a mass lesion invading outside of the left tympanic bulla with osteolysis. Endoscopically assisted ventral bulla osteotomy was performed for tumor resection and definitive diagnosis. Middle ear adenocarcinoma was diagnosed based on histopathology. It appears that these neurological signs occurred due to adenocarcinoma in the tympanic bulla, penetrating the jugular foramen and the hypoglossal canal and damaging the cranial nerve IX (glossopharyngeal nerve), X (vagus nerve), XI (accessory nerve), and XII (hypoglossal nerve) and the sympathetic nerve. To the best of our knowledge, this is the first case report of Villaret's syndrome associated with middle ear adenocarcinoma affecting the nerves passing through the jugular foramen and hypoglossal canal in cats.

Application of carvedilol in a dog with pseudoephedrine toxicosis-induced tachycardia.

A 15-year-old Yorkshire terrier dog was presented after ingesting 1 capsule of an over-the-counter cold medication containing pseudoephedrine (120 mg/capsule) and cetirizine (5 mg/capsule). Treatment was initiated with acepromazine and carvedilol. The dog responded well to treatment. This is the first known case report using carvedilol to control pseudoephedrine toxicosis.