International Journal of Translational Medicine

Cancer stem cells (CSCs) are the cells in a primary tumor that have the opportunity to self-renew as well as differentiate into certain cell types, thus forming a mixed tumor. CSCs have been shown to be involved in every aspect of cancer development, including tumor initiation, proliferation, and metastatic activity; they are also involved in chemotherapeutic drug resistance and the recurrence of certain cancers. Based on these capabilities, CSCs have been explored as the next target for the treatment and management of cancer. Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs. Here we point out the noteworthy work reported on SAL’s mechanism of action, anticancer activities, toxicity, and clinic applications. In addition, SAL derivatives synthesized by different research groups and their biological activity will also be highlighted. Full article

Preeclampsia is an obstetric pathology with striking similarities to COVID-19. The renin-angiotensin system plays a key role in the pathogenesis of both diseases. This report reviews the pharmacological strategies that have been suggested for the prevention and treatment of preeclampsia and that are potentially useful also in the treatment of COVID-19. Of note, both pathologies have in common an Angiotensin II-mediated endothelial dysfunction secondary to an angiogenic imbalance, with effects on vasculature, coagulation, and inflammation. These considerations are drawn from cases of the initial SARS-CoV-2 primary infection and may not apply to more recent SARS-CoV-2 variants or infections after COVID vaccination. The treatment options discussed included albumin infusion, aspirin, corticosteroids, the monoclonal antibody eculizumab, hydroxychloroquine, low molecular weight heparin, magnesium, melatonin, metformin, nitric oxide, proton pump inhibitors, statins, therapeutic apheresis, and vitamin D. Full article

Malaria and HIV are geographically in the tropics and subtropics of the world, including sub-Saharan Africa. Understanding the overlapping effect of both infections, especially among pregnant women, is crucial in managing pregnant women during antenatal care visits, and postpartum babies. It was realized that the prevalence of malaria among HIV-positive pregnant women ranges between 31–61%, while for non-HIV infected pregnant women the prevalence still stands between 10 and 36%. Co-infection is between 0.52 and 56.3%. Even though the rate of mother-to-child transmission of HIV has dropped, MTCT of malaria still remains a problem. MTCT is associated with low birth-weight, anemia, and even immune dysregulation. The adoption of the Option B+ plan has proven to be effective in the fight against the MTCT of HIV. However, malaria in pregnancy still remains a problem. Concurrent administration of both antimalarial drugs and Cotrimozaxole to pregnant women is not recommended, because of the toxic effect of the interaction of both drugs. Nevertheless, studies looking at the effect of the current ART regimens on mothers and their children need to be carried out. Studies looking at exposed children over a longer period of time, to determine their susceptibility to malaria infection and also to monitor their immune response to malaria over time, are needed. Full article

Recently, some drugs were approved to control Monkeypox (MPX), among them tecovirimat. This was recently approved by regulatory agencies around the world, the paper of Zovi et al entitled Pharmacological Agents with Antiviral Activity against Monkeypox Infection highlight it as safe and effective, although the safety data are still not very robust. In this Comment, we present some theoretical evaluations of its safety, considering that for use in humans it is essential to have a rich scientific literature in the area. After a series of analyses, a potential risk of liver, respiratory and kidney damage was found in addition to carcinogenic potential. Thus, while we agree that there is a need for rapid responses to infection, we reinforce that well-designed and adequately powered studies should not only focus on investigating the pharmacological efficacy of tecovirimat but also demonstrate its safety in humans. Therefore, in this Comment, we present some concerns that may help in formulating a safer treatment for patients infected with Monkeypox virus (MPXV). Full article

Depression and obesity are highly comorbid with one another, with evidence of bidirectional causal links between each disorder and a shared biological basis. Genetic factors play a major role in influencing both the occurrence of comorbid depression and obesity, their courses, and their response to existing treatments. The current paper is a scoping review of studies that have evaluated the contribution of specific genetic variants to the comorbidity between obesity and depression. Based on a search of the PubMed and EMBASE databases, 28 studies were included in this review, covering 54 candidate genes. Positive associations were identified for 14 genetic loci (AKR1C2, APOA5, COMT, DAT1, FTO, KCNE1, MAOA, MC4R, MCHR2, NPY2R, NR3C1, Ob, PCSK9, and TAL1). Replicated findings across two or more independent samples were observed for the FTO and MC4R genes. Many of these gene products represent novel molecular targets for the pharmacological management of obesity that interact with each other and are not pharmacologically influenced by existing anti-obesity or antidepressant medications. The implications of these associations for future drug development are discussed, with an emphasis on recent evidence on the polygenic architecture of comorbid depression and obesity and on a precision-medicine approach to these conditions. Full article

Exacerbation of the vascular pathology in radiation retinopathy as a result of pre-existing diabetes has been recognized for many years, as reflected by clinical reports and a few early experimental studies. However, the underlying pathogenetic mechanisms for the synergistic interaction of radiation retinopathy (RR) and diabetic retinopathy (DR) have not been compared and evaluated for insight on this phenomenon. The present work draws attention to the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as common mediators of both conditions and sources of ongoing cellular injury in the radiation-induced bystander effect (RIBE) and the senescence-associated secretory phenotype (SASP). Chronic hyperglycemia-mediated oxidative stress and depleted antioxidant defense in diabetes, together with impaired DNA damage sensing and repair mechanisms, were identified as the primary elements contributing to the increased severity of RR in diabetic patients. We conclude that apart from strategic genetic mutations affecting the DNA damage response (DDR), diabetes represents the most significant common risk factor for vascular injury as a side effect of radiotherapy. Full article

Visceral pain is a unique clinical entity that lacks an effective and safe treatment. Proper preclinical models are essential for assessing new drugs developed for the treatment of this pathology. Few studies report that paclitaxel, an antineoplastic agent, can be used to induce visceral pain in laboratory animals. Our purpose was to investigate the reproducibility of these studies and to develop an animal method that would allow assessing consistent visceral pain. In this study, we used four doses of paclitaxel (3 mg × kg⁻¹; 5 mg × kg⁻¹; 10 mg × kg⁻¹ and 15 mg × kg⁻¹). Visceral pain was evaluated using a scale of abdominal pain immediately after the administration of a single dose of paclitaxel to rats. Tactile and thermal hypersensitivity were assessed using von Frey filaments and the tail flick test initially, at 24 h and 48 h after administration. Rats experienced visceral pain and mechanical and thermal hypersensitivity 24 h after the administration of paclitaxel. The intensity of the pain was increased in a dose-dependent manner with the highest intensity of effect being observed after the administration of a dose of 15 mg × kg⁻¹. Paclitaxel induces visceral pain. The dosage varies depending on the employed strain of rat. This method allows for assessing the efficacy of analgesics to be useful against visceral pain if the paclitaxel dose is adjusted accordingly to the animal strain. Full article

The periodontal disease etiology has been a demesne of scrupulous research, with a myriad of bacterial phylotypes inhabiting the periodontal pockets. The aim of our study was to assess the frequency of Filifactor alocis in type 2 diabetes mellitus (DM) subjects having a healthy periodontium (DH) or chronic periodontitis (DCP) and its correlation with clinical parameters and red complex bacteria. Polymerase chain reaction was carried out for the detection of F. alocis and red complex bacteria from subgingival plaque samples. The data were analyzed using Fisher’s Exact Test and Pearson’s chi-square test. A p value < 0.05 was considered statistically significant. F. alocis was detected at considerably higher levels in DCP (p < 0.05). F. alocis presence was also positively correlated with T. forsythia detection and the clinical parameters PD and CAL (p < 0.05). Subjects with good glycemic control showed a considerably lower detection of F. alocis as compared to fair- and poor-glycemic-control subjects. This is the first paper reporting the co-occurrence of F. alocis and T. forsythia in diabetic subjects with chronic periodontitis. These findings show that F. alocis can play an important role in establishing synergistic collaborations with other pathogenic oral microorganisms and speeding up the course of periodontal disease in diabetics. Full article

COVID-19 is a devastating systemic disease characterized by multisystem involvement driven by exuberant hyperinflammatory and dysregulations in coagulation. In COVID-19 patients, renal failure contributes to morbidity and mortality, and its early detection and timely management are critical to minimize such untoward and irreversible complications. In the healthcare system, family physicians constitute the first node in the management of patients, yet there is a dearth of reports and guidelines focusing on them for specific organ affection. This review provides an overview of recent studies examining the renal manifestations following SARS-CoV-2 infection. We focus on the tell-tale signs and laboratory findings of renal affection in the pediatric and adult populations with COVID-19, specifically for family practitioners to assist in their appropriate triage. Among different manifestations, urinary abnormalities and a modest increase in creatinine are the early indicators of renal affection in COVID-19 patients. Although renal transplant patients are conventionally managed by specialized teams, they may present to family physicians during a pandemic. This review provides a framework for family physicians to promptly detect early indicators of renal involvement in patients infected with SARS-CoV-2, including providing triage guidance for kidney transplant recipients. Full article

Phototherapy using ultraviolet radiation (UVR) treatment units of various designs is common in dermatology. The anatomical distribution of UVR should be even, regardless of individual body shapes. Using electronic dosimeters, we measured the irradiance at 31 body sites on 12 persons of different heights and body mass (BMI). Five different treatment unit designs were tested: cabinet units with standing patients, units with patients lying down, and a unit where patients rotated in front of flatly arranged UVR tubes. In treatment units with short tubes, persons taller than 170 cm received low irradiance on the face, neck, and shoulders. In cabinet-type units, higher BMI lowered the irradiance on the chest and belly. The relative standard deviation (RSD) of irradiance was smallest for the rotating unit, and for the unit with patients lying down while irradiated from above only. A higher RSD was found in the unit designs where patients stood inside cabinets, and where patients lay down and were simultaneously irradiated from both sides. In general, longer tubes lower the overall RSD. The irradiance of the different body areas is about 60% of the measured calibration values, but to avoid provoking any erythema, the treatment dose can only be increased by 10%. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing global incidence. Morbidity and mortality associated with HCC remains high, and HCC is the leading cause of cancer death worldwide. Early detection and treatment of HCC can increase five-year survival by over 60%. Detection of HCC remains challenging, however, as HCC arises from a variety of environmental, genetic, and viral etiologies, and it demonstrates a complex pathophysiology and displays a heterogeneous morphology. Current diagnostic methods rely on abdominal ultrasound with or without concurrent AFP biomarker testing for high-risk individuals. This review provides an overview of HCC diagnostic modalities and highlights the promising nature of translational developments in biomarkers, next generation sequencing (NGS), artificial intelligence, molecular imaging, and liquid biopsy for earlier and more accurate diagnosis of HCC. Furthermore, we identify areas for improvement that must be addressed before the widespread usage and implementation of these methods. Full article

Throughout their life, women should pay attention to their mental health. Evidence indicates that poor sleep quality is related to depressive symptoms in pregnancy, justifying the intervention of health professionals in improving sleep quality to promote the mental health of pregnant women. The objective of our study is to analyze the relationship between sleep quality and perinatal depression, and to identify the obstetric nurse’s intervention in improving sleep quality in the perinatal period. A total of 53 pregnant women between the 28th week of pregnancy and the 7th day after delivery completed the Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI). Women were also asked about the strategies used by the obstetric nurse to improve their quality of sleep. Data analysis was performed using IBM SPSS Statistics software, version 25.0. The Mann–Whitney-U and Kruskal-Wallis tests were carried out. A p-value < 0.05 was considered statistically significant. The median PSQI score was 10 (±3.63), and 9.2% (n = 9) had good quality sleep. The median EPDS score was 12 (±4.43), and 27 participants (50.9%) had probable depression. The women with likely depression had worse sleep quality (p = 0.016). Most participants reported that the obstetric nurse showed no interest in their sleep quality during pregnancy. Women of other nationalities have a higher risk of depression (p = 0.013). Based on our results, it is crucial to assess sleep quality in the perinatal period to promote women’s health during the prenatal and postnatal periods, and more action is needed since we are facing one of the most significant challenges of this century, preventing depression. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds are under clinical investigation for various diseases. In particular, marine natural compounds are gaining more attention in the new drug development process. The present study aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the 4 SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds, namely, chrysophaentin A (−6.6 kcal/mol), geodisterol sulfates (−6.6 kcal/mol), hymenidin (−6.4 kcal/mol), plinabulin (−6.4 kcal/mol), and tetrodotoxin (−6.3 kcal/mol) expressed minimized binding energy and molecular interactions, such as covalent and hydrophobic interactions, with the SARS CoV-2 main protease. Using molecular dynamic studies, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (ROG), and hydrogen bond (H-Bond) values were calculated for the SARS-CoV-2 main protease with a hymenidin docked complex. Additionally, in silico drug-likeness and pharmacokinetic property assessments of the compounds demonstrated favorable druggability. These results suggest that marine natural compounds are capable of fighting SARS-CoV-2. Further in vitro and in vivo studies need to be carried out to confirm their inhibitory potential. Full article

Peer Victimization (PV) or being bullied in childhood/adolescence has been associated with several negative outcomes in mental health conditions beyond the time of its occurrence. However, its possible association with personality disorders has been slightly explored. In the present study we have compared the frequency of DSM IV personality disorders among adult patients with (N = 28) or without (N = 418) a reported history of PV. For this purpose, axis II was evaluated with the Self-Report Checklist for Preliminary Items for Major Categories, whereas self-esteem and self-assessment of functioning were evaluated with single questions. Patients with PV history have met the diagnostic criteria of the avoidant (60.7% vs. 12.2%), depressive (28.5% vs. 5.2%) and paranoid (17.9% vs. 5%) personality disorders more frequently than patients without history of PV. Moreover, these patients with antecedents of being bullied have also reported lower self-esteem (2 vs. 3) and in the assessment of social functioning (4 vs. 5). Our study indicated that there is a clear association between PV and avoidant, depressive and paranoid personality patterns. These results suggest that the stress related with the experience of PV threatens a basic psychobiological need such as social acceptance with implications for the beginning of long-term dysfunctional personality trajectories. Full article

Estimating the basic reproduction number (R₀) of an infectious disease is a crucial step to describe the contagiousness and provides suggestions for interventions. To lift the effectiveness of preventive measures for the COVID-19 pandemic, we need to minimize the newly infected cases by reaching adequate herd immunity. This study thus aimed to compare the R₀ through four waves of COVID-19 outbreaks in Vietnam and to calculate the minimal vaccination coverage in different populations. The data on the number of daily confirmed COVID-19 patients were collected from 21 January 2020 to 16 November 2021 from the daily reports through the four waves of the pandemic in Vietnam. The R₀ values were estimated by exponential growth and the maximum likelihood methods to range from 1.04 to 3.31 from the first to the third wave. The fourth wave was the most severe, especially in the southern provinces, and the highest R₀ was in Ho Chi Minh City. The herd immunity would range from 43.50% to 95.76% by various R₀ values from different populations. Overall, the presence of new viral mutants increased the infectiousness and the vaccination coverage was higher to establish the required herd immunity in a high-density population. The results provide the basis for policy recommendations and resource allocation for vaccine management and distribution at a time when the COVID-19 pandemic is not yet over. Full article

Background: Radiation or hormonal therapy is considered for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, these therapies have their own complications. To delay the start of these therapies, we investigated the efficacy and safety of Brazilian green propolis for the treatment for BCR after RP. Materials and Methods: This single-center, single-arm open trial included 22 patients who experienced BCR after RP between 2016 and 2019. The patients received nine softgels of Brazilian green propolis (containing 40 mg propolis per capsule) daily for 6 months. The primary outcome was the prostate-specific antigen (PSA) response rate. The secondary outcomes included progression-free time, PSA slope (1/PSA doubling time) response rate, quality of life, and safety profile. Results: The PSA response rate was 0%. The mean PSA slopes before and after baseline were 0.12 month⁻¹ and 0.08 month⁻¹, respectively. Fifteen patients (68%) showed a decreased PSA slope after treatment. There were no negative effects on quality of life or serious adverse events leading to treatment discontinuation. Conclusion: There was no significant anticancer response in patients who received Brazilian green propolis. However, the PSA slope was decreased after propolis administration. Further, Brazilian green propolis may be safely consumed by patients. Full article

Plant secondary metabolites are well-recognized medicinally important compounds. Gossypol is an important plant secondary metabolite with several medicinal properties. Carbon nanotubes (CNTs) are allotropes of carbon with diverse applicability in chemical, physical, and biological sciences due to their high surface area. The current study demonstrates the enhancement of gossypol production in cotton cell suspension culture in culture media supplemented with water-soluble carbon nanotubes. The fresh and dry weights of cotton cell suspension culture grown in MS media with 20 µg/mL CNTs were, respectively, 1.9 and 2.13 fold higher than in control MS media after one month. The net enhancement of gossypol production in MS media supplemented with 20 µg/mL CNTs was 2.47 fold higher than the control. Confocal and SEM imaging showed the presence CNTs on the cell surface, which mediated the formation of extra channels that resulted in high biomass production in cotton cell suspension culture. The gossypol produced by this cell suspension culture showed antiproliferative activity against the prostate cancer cell line. Thus, this study demonstrated a new method for enhanced gossypol production, which can prove beneficial for the production of other plant-based biological active compounds. Full article

IgA Vasculitis (IgAV) is the most common form of vasculitis in children, and 1–2% of patients develop chronic kidney disease. In other forms of glomerulonephritis, there is strong evidence to support the role of the renin-angiotensin-aldosterone system (RAAS); however, data are lacking in IgAV nephritis. This study evaluated urinary RAAS components in children with IgA vasculitis, both with nephritis (IgAVN) and without nephritis (IgAVwoN). Urinary concentrations of renin, angiotensinogen and aldosterone were quantified using ELISAs. In total, 40 patients were included: IgAVN n = 9, IgAVwoN n = 17, HC n = 14, with a mean age of 8.3 ± 3.3 years. Urinary renin demonstrated no trend with nephritis. Urinary angiotensinogen was statistically significantly elevated in IgAV (1.18 ± 1.16 ng/mmol) compared to HC (0.28 ± 0.27 ng/mmol, p = 0.0015), and IgAVN (2.00 ± 1.22 ng/mmol) was elevated compared to IgAVwoN (0.74 ± 0.89 ng/mmol, p = 0.0492) and HC (p = 0.0233). Urinary aldosterone levels were significantly elevated in IgAV (1236 ± 1438 pg/mmol) compared to HC (73.90 ± 65.22 pg/mmol, p < 0.0001); this was most increased in IgAVwoN patients (1793 ± 1507 pg/mmol; IgAVN 183.30 ± 111.30 pg/mmol, p = 0.0035, HC p < 0.0001). As expected, the RAAS system is activated in patients with IgAVN and, more surprisingly, even in those without active nephritis. Further studies are needed to fully understand the role of the RAAS system in IgA vasculitis. Full article