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.

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.

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.

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.

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.

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.

Case Report: Hindlimb Ataxia Concurrent With Seizures by Presumed Osmotic Demyelination Syndrome in a Dog.

A 6-year-old castrated male Chihuahua dog was presented with hindlimb paresis and ataxia. The dog had hyponatremia and was diagnosed as hypoadrenocorticism 10 days before its visit, and the neurologic signs including generalized tonic seizures and hindlimb paresis occurred 3 days after correction of hyponatremia at a referral hospital. Based on history and clinical findings, osmotic demyelination syndrome (ODS) secondary to rapid correction of hyponatremia was highly suspected. After administration of anti-convulsant and supplements, seizures did not occur, and gait was normalized within 2 weeks. Phenobarbital was tapered and finally discontinued after 3 months, and seizure did not recur. The neurologic signs were completely resolved and the dog continued to be free of neurologic or additional clinical signs over the 19-month follow-up period. ODS should be included among the differential diagnoses in case of any acute neurological dysfunction that occurs with episodes of rapid correction of hyponatremia. To the author's knowledge, this is the rare case report of a dog with hypoadrenocorticism and presumed ODS after rapid correction of hyponatremia leading to neurologic signs including seizures and ataxia.

The role of extracellular vesicles in animal reproduction and diseases.

Extracellular vesicles (EVs) are nanosized membrane-enclosed compartments that serve as messengers in cell-to-cell communication, both in normal physiology and in pathological conditions. EVs can transfer functional proteins and genetic information to alter the phenotype and function of recipient cells, which undergo different changes that positively affect their structural and functional integrity. Biological fluids are enriched with several subpopulations of EVs, including exosomes, microvesicles (MVs), and apoptotic bodies carrying several cargoes, such as lipids, proteins, and nucleic acids. EVs associated with the reproductive system are actively involved in the regulation of different physiological events, including gamete maturation, fertilization, and embryo and fetal development. EVs can influence follicle development, oocyte maturation, embryo production, and endometrial-conceptus communication. EVs loaded with cargoes are used to diagnose various diseases, including pregnancy disorders; however, these are dependent on the type of cell of origin and pathological characteristics. EV-derived microRNAs (miRNAs) and proteins in the placenta regulate inflammatory responses and trophoblast invasion through intercellular delivery in the placental microenvironment. This review presents evidence regarding the types of extracellular vesicles, and general aspects of isolation, purification, and characterization of EVs, particularly from various types of embryos. Further, we discuss EVs as mediators and messengers in reproductive biology, the effects of EVs on placentation and pregnancy disorders, the role of EVs in animal reproduction, in the male reproductive system, and mother and embryo cross-communication. In addition, we emphasize the role of microRNAs in embryo implantation and the role of EVs in reproductive and therapeutic medicine. Finally, we discuss the future perspectives of EVs in reproductive biology.

Comparative analysis of mesenchymal stem cells cultivated in serum free media.

Stem cells are attractive candidates for the regeneration of tissue and organ. Mesenchymal stem cells (MSCs) have been extensively investigated for their potential applications in regenerative medicine and cell therapy. For developing effective stem cell therapy, the mass production of consistent quality cells is required. The cell culture medium is the most critical aspect of the mass production of qualified stem cells. Classically, fetal bovine serum (FBS) has been used as a culture supplement for MSCs. Due to the undefined and heterologous composition of animal origin components in FBS, efforts to replace animal-derived components with non-animal-derived substances led to safe serum free media (SFM). Adipose derived mesenchymal stem cells (ADSCs) cultivated in SFM provided a more stable population doubling time (PDT) to later passage and more cells in a shorter time compared to FBS containing media. ADSCs cultivated in SFM had lower cellular senescence, lower immunogenicity, and higher genetic stability than ADSCs cultivated in FBS containing media. Differential expression analysis of mRNAs and proteins showed that the expression of genes related with apoptosis, immune response, and inflammatory response were significantly up-regulated in ADSCs cultivated in FBS containing media. ADSCs cultivated in SFM showed similar therapeutic efficacy in an acute pancreatitis mouse model to ADSCs cultivated in FBS containing media. Consideration of clinical trials, not only pre-clinical trial, suggests that cultivation of MSCs using SFM might offer more safe cell therapeutics as well as repeated administration due to low immunogenicity.

Case Report: Aortic Regurgitation of Postocclusion and Long-Term Outcome Following PDA Correction in an Adult Dog.

A 9-year-old intact female Maltese dog was admitted for further evaluation of previously diagnosed patent ductus arteriosus (PDA). The dog showed severe coughing and exercise intolerance. On physical examination, a grade VI/VI continuous heart murmur was auscultated. Thoracic radiography demonstrated cardiomegaly, pulmonary overcirculation, and moderate bronchointerstitial pattern. Echocardiography revealed severe dilation of the left ventricle and atrium, decreased left ventricular contractility, and left-to-right PDA. On electrocardiography (ECG), R amplitude was increased. Computed tomographic angiography revealed type IIA PDA. The serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration was >10,000 pmol/L. Transarterial occlusion was performed and the Amplatz® Canine Duct Occluder was successfully deployed. On echocardiography 48 h after the procedure, aortic regurgitation (AR) and residual ductal flow were noted. Long-term follow-up on clinical signs, physical examination, radiography, echocardiography, ECG, and serum NT-proBNP were evaluated until 30 months after correction of PDA. The clinical indices of physical examination, thoracic radiography, echocardiography, ECG, and serum NT-proBNP concentration were improved, although the postocclusion AR and residual ductal flow persisted. The dog followed up without clinical signs for 41 months following the correction. To our knowledge, this is the first case report to demonstrate quite a long time of follow-up (41 months) in an older dog with transarterial occlusion of PDA with postocclusion AR and residual flow.

Circulating Galectin-3 Evaluation in Dogs With Cardiac and Non-cardiac Diseases.

Galectin-3 is involved in important biological functions such as fibrogenesis and inflammation. Notably, it is associated with various diseases and plays a major role in cardiac inflammation and fibrosis. Although heart diseases are relatively common in dogs, a few studies have analyzed the circulating galectin-3 concentration in dogs with various heart diseases, including myxomatous mitral valve disease, patent ductus arteriosus, and pulmonic stenosis. The aims of the present study were to evaluate the effect of heart disease on circulating galectin-3 levels in dogs, and also to evaluate the correlation between galectin-3 concentration and conventional echocardiographic indices along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in dogs with heart diseases. The medical records and archived serum samples of 107 dogs were evaluated retrospectively. In total, 107 dogs were classified into healthy dogs (n = 8), cardiac disease (n = 26), and non-cardiac disease groups (n = 73). The circulatory galectin-3 levels were analyzed using a commercially available canine-specific galectin-3 enzyme-linked immunosorbent assay kit. This study demonstrated that dogs with heart, endocrine, and dermatologic diseases had significantly higher galectin-3 levels than healthy dogs (p = 0.009, p = 0.007, and p = 0.026, respectively). Among dogs with heart diseases, dogs with concentric cardiomyopathy had significantly increased circulatory galectin-3 levels compared with healthy dogs (p = 0.028). E'/A' had a positive association with galectin-3 levels among conventional echocardiographic indices. Moreover, the galectin-3 concentration could predict diastolic dysfunction. In dogs with myxomatous mitral valve disease, a significantly positive correlation was revealed between galectin-3 levels and NT-proBNP levels (p = 0.007). Overall, this study demonstrates that circulatory galectin-3 levels increase in dogs with heart, endocrine, and dermatologic diseases. Moreover, this study demonstrates that galectin-3 concentration could be helpful to evaluate cardiac remodeling and diastolic function. Further large-scale research is required to evaluate the role of circulating galectin-3 in dogs with heart diseases.

Identification and Characterization of Circulating MicroRNAs as Novel Biomarkers in Dogs With Heart Diseases.

Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases. Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis. Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.

Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.

Repurposing Kinase Inhibitor Bay 11-7085 to Combat Staphylococcus aureus and Candida albicans Biofilms.

Staphylococcus aureus and Candida spp. are commonly linked with topical biofilm-associated infections such as those found on chronic wounds. These biofilms are notoriously difficult to treat, highlighting the grave need to discover and study new broad-spectrum agents to combat associated infections. Here we report that the kinase inhibitor Bay 11-7085 exhibited bactericidal activity against multidrug-resistant S. aureus with a minimum inhibitory concentration (MIC) of 4 µg/ml. In addition, S. aureus strain MW2 did not acquire resistance to antibiotic pressure. Furthermore, Bay 11-7085 exhibited potency against Candida albicans and the emerging pathogen Candida auris with a MIC of 0.5-1 µg/ml. Bay 11-7085 partially inhibited and eradicated biofilm formation of various pathogens, such as VRSA (vancomycin-resistant S. aureus), as well as antifungal-resistant Candida spp. isolates. Notably, Bay 11-7085 partially inhibited initial cell attachment and formation of a VRSA-C. albicans polymicrobial biofilm in vitro. In contrast to C. albicans, inhibition of VRSA biofilm was linked to initial cell attachment independent of its bactericidal activity. Finally, Bay 11-7085 was effective in vivo at increasing the lifespan of C. elegans during an S. aureus and a C. albicans infection. Our work proposes kinase inhibitor Bay 11-7085 as a potential compound capable of combating biofilms associated with primary multidrug-resistant bacteria and yeast pathogens associated with wound infections.

Biogenesis, Membrane Trafficking, Functions, and Next Generation Nanotherapeutics Medicine of Extracellular Vesicles.

Extracellular vesicles (EVs) are a heterogeneous group of membrane-limited vesicles and multi-signal messengers loaded with biomolecules. Exosomes and ectosomes are two different types of EVs generated by all cell types. Their formation depends on local microdomains assembled in endocytic membranes for exosomes and in the plasma membrane for ectosomes. Further, EV release is a fundamental process required for intercellular communication in both normal physiology and pathological conditions to transmit/exchange bioactive molecules to recipient cells and the extracellular environment. The unique structure and composition of EVs enable them to serve as natural nanocarriers, and their physicochemical properties and biological functions can be used to develop next-generation nano and precision medicine. Knowledge of the cellular processes that govern EVs biology and membrane trafficking is essential for their clinical applications. However, in this rapidly expanding field, much remains unknown regarding EV origin, biogenesis, cargo sorting, and secretion, as well as EV-based theranostic platform generation. Hence, we present a comprehensive overview of the recent advances in biogenesis, membrane trafficking, and functions of EVs, highlighting the impact of nanoparticles and oxidative stress on EVs biogenesis and release and finally emphasizing the role of EVs as nanotherapeutic agents.

Expression Profile of Circulating MicroRNAs in Dogs With Cardiac Hypertrophy: A Pilot Study.

This study aimed to identify the expression profile of circulating microRNAs in dogs with eccentric or concentric cardiac hypertrophy. A total of 291 microRNAs in serum samples of five dogs with myxomatous mitral valve degeneration (MMVD) and five dogs with pulmonic stenosis (PS) were compared with those of five healthy dogs using microarray analysis. Results of microarray analysis revealed up-regulation of cfa-miR-130b [fold change (FC) = 2.13, p = 0.014), down-regulation of cfa-miR-375 (FC = 1.51, p = 0.014), cfa-miR-425 (FC = 2.56, p = 0.045), cfa-miR-30d (FC = 3.02, p = 0.047), cfa-miR-151 (FC = 1.89, p = 0.023), cfa-miR-19b (FC = 3.01, p = 0.008), and cfa-let-7g (FC = 2.53, p = 0.015) in MMVD group which showed eccentric cardiac hypertrophy, up-regulation of cfa-miR-346 (FC = 2.74, p = 0.032), down-regulation of cfa-miR-505 (FC = 1.56, p = 0.016) in PS group which showed concentric cardiac hypertrophy, and down-regulation of cfa-miR-30c (FC = 3.45, p = 0.013 in MMVD group; FC = 3.31, p = 0.014 in PS group) and cfa-let-7b (FC = 11.42, p = 0.049 in MMVD group; FC = 5.88, p = 0.01 in PS group) in both MMVD and PS groups. In addition, the unsupervised hierarchical clustering of differentially expressed microRNAs in each group resulted in complete separation of healthy dogs from dogs with heart diseases. Therefore, eleven microRNAs among 291 microRNAs were identified as differentially expressed circulating microRNAs related to MMVD or PS in dogs. This pilot study demonstrates that the microRNAs identified in this study could be possible candidates for novel biomarker or therapeutic target related to cardiac hypertrophy in dogs.

Palladium Nanoparticle-Induced Oxidative Stress, Endoplasmic Reticulum Stress, Apoptosis, and Immunomodulation Enhance the Biogenesis and Release of Exosome in Human Leukemia Monocytic Cells (THP-1).

BACKGROUND: Exosomes are endosome-derived nano-sized vesicles that have emerged as important mediators of intercellular communication and play significant roles in various diseases. However, their applications are rigorously restricted by the limited secretion competence of cells. Therefore, strategies to enhance the production and functions of exosomes are warranted. Studies have shown that nanomaterials can significantly enhance the effects of cells and exosomes in intercellular communication; however, how palladium nanoparticles (PdNPs) enhance exosome release in human leukemia monocytic cells (THP-1) remains unclear. Therefore, this study aimed to address the effect of PdNPs on exosome biogenesis and release in THP-1 cells. METHODS: Exosomes were isolated by ultracentrifugation and ExoQuickTM and characterized by dynamic light scattering, nanoparticle tracking analysis system, scanning electron microscopy, transmission electron microscopy, EXOCETTM assay, and fluorescence polarization. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: PdNP treatment enhanced the biogenesis and release of exosomes by inducing oxidative stress, endoplasmic reticulum stress, apoptosis, and immunomodulation. The exosomes were spherical in shape and had an average diameter of 50-80 nm. Exosome production was confirmed via total protein concentration, exosome counts, acetylcholinesterase activity, and neutral sphingomyelinase activity. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in PdNP-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from PdNP-treated THP-1 cells than in those isolated from control cells. THP-1 cells pre-treated with N-acetylcysteine or GW4869 showed significant decreases in PdNP-induced exosome biogenesis and release. CONCLUSION: To our knowledge, this is the first study showing that PdNPs stimulate exosome biogenesis and release and simultaneously increase the levels of cytokines and chemokines by modulating various physiological processes. Our findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications.

Role and Therapeutic Potential of Melatonin in Various Type of Cancers.

Cancer is a large group of diseases and the second leading cause of death worldwide. Lung, prostate, colorectal, stomach, and liver cancers are the most common types of cancer in men, whereas breast, colorectal, lung, cervical, and thyroid cancers are the most common among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, and immunotherapy, have been used as conventional treatments for patients with cancer. However, the clinical outcomes of advanced-stage disease remain relatively unfavorable owing to the emergence of chemoresistance, toxicity, and other undesired detrimental side effects. Therefore, new therapies to overcome these limitations are indispensable. Recently, there has been considerable evidence from experimental and clinical studies suggesting that melatonin can be used to prevent and treat cancer. Studies have confirmed that melatonin mitigates the pathogenesis of cancer by directly affecting carcinogenesis and indirectly disrupting the circadian cycle. Melatonin (MLT) is nontoxic and exhibits a range of beneficial effects against cancer via apoptotic, antiangiogenic, antiproliferative, and metastasis-inhibitory pathways. The combination of melatonin with conventional drugs improves the drug sensitivity of cancers, including solid and liquid tumors. In this manuscript, we will comprehensively review some of the cellular, animal, and human studies from the literature that provide evidence that melatonin has oncostatic and anticancer properties. Further, this comprehensive review compiles the available experimental and clinical data analyzing the history, epidemiology, risk factors, therapeutic effect, clinical significance, of melatonin alone or in combination with chemotherapeutic agents or radiotherapy, as well as the underlying molecular mechanisms of its anticancer effect against lung, breast, prostate, colorectal, skin, liver, cervical, and ovarian cancers. Nonetheless, in the interest of readership clarity and ease of reading, we have discussed the overall mechanism of the anticancer activity of melatonin against different types of cancer. We have ended this report with general conclusions and future perspectives.

Correction: Gurunathan, S. et al. Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes. Cells 2019, 8, 307.

In the original review [...].

Human endogenous retrovirus-enveloped baculoviral DNA vaccines against MERS-CoV and SARS-CoV2.

Here we report a recombinant baculoviral vector-based DNA vaccine system against Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). A non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) was constructed as a DNA vaccine vector for gene delivery into human cells. For MERS-CoV vaccine construction, DNA encoding MERS-CoV S-full, S1 subunit, or receptor-binding domain (RBD) was inserted into the genome of AcHERV. For COVID19 vaccine construction, DNA encoding SARS-CoV2 S-full or S1 or a MERS-CoV NTD domain-fused SARS-CoV2 RBD was inserted into the genome of AcHERV. AcHERV-DNA vaccines induce high humoral and cell-mediated immunity in animal models. In challenge tests, twice immunized AcHERV-MERS-S1 and AcHERV-COVID19-S showed complete protection against MERS-CoV and SARS-CoV2, respectively. Unlike AcHERV-MERS vaccines, AcHERV-COVID19-S provided the greatest protection against SARS-CoV2 challenge. These results support the feasibility of AcHERV-MERS or AcHERV-COVID19 vaccines in preventing pandemic spreads of viral infections.