Life

This study aimed to investigate the anti-atherosclerotic properties of quercetin isolated from the extract of Hedysarum neglectum Ledeb hairy roots. During the study, the hormonal composition of the nutrient medium for cultivation of H. neglectum hairy root biomass was selected: Gamborg’s medium enriched with the cytokine 6-benzylaminopurine (1.5 mg/1 dm³). It was found that the extraction of hairy root biomass with a 50% water–ethanol solution (40:1 1 h at 60 ± 2 °C) yielded an extract that contained the highest amount of quercetin (an average of 2.1 times higher than in extracts obtained at other parameters). It was determined that 100 µM quercetin solution showed the greatest bioactivity on Caenorhabditis elegans: on day 61, the percentage of surviving nematodes was 2.06 times higher compared to other samples and 6 times higher compared to control, resulting in a 12.5-fold increase in SOD-3 expression compared to control (without biologically active substance (BAS) addition). Meanwhile, the 10 µM quercetin solution exhibited the best ability to inhibit the accumulation of lipid fractions; the accumulation was 1.06 times less compared to the control. The results of this study show that quercetin, which was isolated from the biomass of H. neglectum hairy roots, can be used as a component of anti-atherosclerotic dietary supplements. Full article

Mpox has caused a global outbreak since May 2022, particularly affecting people belonging to key populations, but cases among healthcare providers have been reported. The aim of this work is to present the experience of the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy with respect to infection control and prevention of mpox occupational transmission. Between May–November 2022, 140 individuals were diagnosed with mpox and six required hospitalization. Overall, 12 medical doctors and 22 nurses provided care to people with mpox. A hospital policy aimed at controlling viral transmission was implemented in May 2022. Protective equipment was used for all healthcare providers. One accidental puncture occurred with a scalpel contaminated with blood from a mpox viremic individual (mpox plasma cycle threshold = 36); no mpox related symptoms were observed and mpox testing ruled out transmission. Six months following exposure, neutralizing antibodies were not detectable, ruling out contagion. Overall, we observed no mpox transmission among healthcare workers, despite the number of visits and procedures performed, including bodily-fluids sampling, and even following puncture with contaminated blood. Hospital preparedness for the management of new infectious disease outbreaks, with rapid implementation of policies aimed at controlling infection, is paramount to avoid occupational transmission. Full article

Obesity has received increasing attention in recent years because it is a factor in the development of non-communicable diseases. The current study aimed to analyze how representative fatty acids (FAs) such as palmitic acid, stearic acid, oleic acid, α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) affected adipogenesis when/if introduced at the differentiation stage of 3T3-L1 cell culture. These FAs are assumed to be potentially relevant to the progression or prevention of obesity. EPA added during the differentiation stage reduced intracellular triacylglycerol (TAG) accumulation, as well as the expression of the established adipocyte-specific marker genes, during the maturation stage. However, no other FAs inhibited intracellular TAG accumulation. Coexistence of Δ¹²-prostaglandin J₂, a peroxisome proliferator-activated receptor γ activator, with EPA during the differentiation stage partially attenuated the inhibitory effect of EPA on intracellular TAG accumulation. EPA increased cyclooxygenase-2 (COX-2) expression and protein kinase A (PKA) activity at the differentiation stage, which could explain the inhibitory actions of EPA. Taken together, exposure of preadipocytes to EPA only during the differentiation stage may be sufficient to finally reduce the mass of white adipose tissue through increasing COX-2 expression and PKA activity. Full article

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are a major healthcare challenge worldwide. Disturbances in the immune system and gut microbiota followed by environmental triggers are thought to be part of the aetiological factors. Current treatment for IBD includes corticosteroids, immunosuppressants, and other biologic agents; however, some patients are still unresponsive, and these are also linked to high financial load and severe side effects. Plant-derived natural products are rich in phytochemicals and have been used as healing agents in several diseases since antiquity due to their antioxidant, anti-inflammatory, and immunomodulatory properties, as well as gut microbiota modulation. Numerous in vitro and in vivo studies have shown that phytochemicals act in key pathways that are associated with the pathogenesis of IBD. It is also reported that the use of plant-derived natural products as complementary treatments is increasing amongst patients with IBD to avoid the side effects accompanying standard medical treatment. This review summarises the relevant evidence around the use of plant-derived natural products in the management of IBD, with specific focus on the clinical evidence so far for Curcumin, Mastiha, Boswellia serrata, and Artemisia absinthium. Full article

Information regarding the longitudinal effects of natural/environmental disasters on obstetrics outcomes is limited. This study aimed to analyze the longitudinal changes in obstetrics outcomes over 8 years after the Great East Japan Earthquake and the Fukushima power plant accident. We used data from the first 8 years of the Pregnancy and Birth Survey by the Fukushima prefectural government, launched in 2011. We compared data on obstetrics outcomes by year and divided Fukushima Prefecture into six districts based on administrative districts. Longitudinal changes in the occurrence of preterm birth before 37 gestational weeks, low birth weight, and anomalies in newborns were accessed using the Mantel–Haenszel test for trends in all six districts. Overall, 57,537 participants were included. In 8 years, maternal age, conception rate after sterility treatment, and cesarean section delivery incidence increased. Although significant differences were observed in preterm birth and low birth weight occurrence among districts, there was no significant trend in the occurrence of preterm birth, low birth weight, and anomalies in newborns in all six districts of Fukushima Prefecture. The Great East Japan Earthquake and Fukushima power plant accident were associated with increased cesarean section delivery incidence but had no significant adverse effects on obstetrics outcomes. Full article

Positron emission tomography (PET) is an imaging modality used for the noninvasive assessment of tumor staging and response to therapy. PET with ¹⁸F labeled fluorodeoxyglucose (¹⁸F-FDG PET) is widely used to assess the active and inactive lesions in patients with multiple myeloma (MM). Despite the availability of ¹⁸F-FDG PET for the management of MM, PET imaging is less sensitive than next-generation flow cytometry and sequencing. Therefore, the novel PET radiotracers ⁶⁴Cu-LLP2A, ⁶⁸Ga-pentixafor, and ⁸⁹Zr-daratumumab have been developed to target the cell surface antigens of MM cells. Furthermore, recent studies attempted to visualize the tumor-infiltrating lymphocytes using PET imaging in patients with cancer to investigate their prognostic effect; however, these studies have not yet been performed in MM patients. This review summarizes the recent studies on PET with ¹⁸F-FDG and novel radiotracers for the detection of MM and the resulting preclinical research using MM mouse models and clinical studies. Novel PET technologies may be useful for developing therapeutic strategies for MM in the future. Full article

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as urologic pain or discomfort in the pelvic region, associated with urinary symptoms and/or sexual dysfunction, lasting for at least 3 of the previous 6 months. The rate of symptoms related to prostatitis has a mean prevalence of 8–8.2%. CP/CPPS is most frequent in men younger than 50 years, among whom it is the most common urologic diagnosis. In the last decades, many studies have been published on CP/CPPS and its association with male infertility. The pathophysiologic relation between CP/CPPS and male infertility involves several aspects, which are not well studied yet. A reduction in semen parameters has been demonstrated in patients with CP/CPPS, and several mechanisms have been proposed to represent putative pathophysiological links between CP/CPPS and infertility, including male accessory gland inflammation, metabolic syndrome, inflammatory bowel disease, HPV co-infection and autoimmunity. In light of this evidence, a multidisciplinary approach is advocated for patients with known CP/CPPS, and particular attention is needed for male patients of infertile couples in order to evaluate male accessory glands correctly. In addition, it is advisable that future studies dealing with the treatment of CP/CPPS take into consideration all the different pathophysiological aspects implicated. Full article

Thromboprophylaxis is a mainstay of treatment of hospitalized COVID-19 patients, due to the high occurrence of thrombotic events. This increases the risk of bleeding. However, data on bleeding events and associated risk factors are scarce. Thus, we aimed to investigate the incidence, predictors and clinical outcomes associated with major bleeding in hospitalized COVID-19 patients. We retrospectively evaluated a cohort of 4014 consecutively hospitalized COVID-19 patients treated in a tertiary-level institution in the period 3/2020–3/2021. Bleeding of any kind was documented in 322 (8%) and major bleeding in 129 (3.2%) patients. A total of 129 (40.1%) bleeding events were present at the time of hospital admission, and 193 (59.9%) occurred during hospitalization. In the multivariate logistic regression analysis, intensive-care-unit treatment (adjusted odds ratio (aOR) 6.55; p < 0.001), atrial fibrillation (aOR 2.55; p = 0.029), higher white-blood-cell count (WBC) (aOR 1.03; p = 0.021), lower hemoglobin (aOR 0.97; p = 0.002) and history of bleeding (aOR 17.39; p < 0.001) were recognized as mutually independent predictors of major bleeding. Major bleeding was significantly associated with increased in-hospital mortality compared to non-major-bleeding patients (59.7% vs. 34.8%, p < 0.001), especially if occurring during hospitalization. Median time from major bleeding to death was 5 days. Bleeding events are frequent in hospitalized COVID-19 patients, with a significant proportion of patients presenting at the time of hospital admission, and others almost universally exposed to anticoagulant and corticosteroid therapies. Major bleeding is associated with high mortality, especially if occurring during hospitalization. The recognition of patients at risk and implementation of timely interventions are of high clinical importance. Full article

The female micro-wasp in mid-Cretaceous Burmese amber is described as a new genus and species in the extinct family Caradiophyodidae fam. nov. (Hymenoptera: Platygastroidea). Features of the specimen are its small body size (1.3 mm), no elbows, elongated, 15-segmented antennae, a deep cleft in the top of its head, a tarsal formula of 5-5-5, a reduced venation with a small pterostigma but no uncus in the forewing, no anal lobe in the hind wing, and a possible coiled ovipositor in the metasoma. Large unidentified expanded structures, considered to be possible seeds, plant secretions, or host eggs, are attached to each antenna. Full article

Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (β: −0.13) was found. This association was modified by the subjects’ race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (β: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (β: −3.11) and central area (β: −3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race. Full article

Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the current review with an eye toward potential therapeutic treatments. LncRNAs are remarkably adaptable, acting as scaffolding, guides, or decoys to modify key signaling pathways (i.e., the Wnt/β-catenin pathway) and gene expression. As post-transcriptional gatekeepers, miRNAs control gene expression by attaching to messenger RNAs and causing their degradation or suppression during translation. Cell cycle regulation, cellular differentiation, and immunological responses are all affected by the dysregulation of miRNAs observed in skin cancer. NcRNAs also show promise as diagnostic biomarkers and prognostic indicators. Unraveling the complexity of the regulatory networks governed by ncRNAs in skin cancer offers unprecedented opportunities for groundbreaking targeted therapies, revolutionizing the landscape of dermatologic care. Full article

With the increasing demand for medicinal plants and the increasing shortage of resources, improving the quality and yield of medicinal plants and making more effective use of medicinal plants has become an urgent problem to be solved. During the growth of medicinal plants, various adversities can lead to nutrient loss and yield decline. Using traditional chemical pesticides to control the stress resistance of plants will cause serious pollution to the environment and even endanger human health. Therefore, it is necessary to find suitable pesticide substitutes from natural ingredients. As an important part of the microecology of medicinal plants, endophytes can promote the growth of medicinal plants, improve the stress tolerance of hosts, and promote the accumulation of active components of hosts. Endophytes have a more positive and direct impact on the host and can metabolize rich medicinal ingredients, so researchers pay attention to them. This paper reviews the research in the past five years, aiming to provide ideas for improving the quality of medicinal plants, developing more microbial resources, exploring more medicinal natural products, and providing help for the development of research on medicinal plants and endophytes. Full article

Duodenoscope-related infections are a major concern in medicine and GI endoscopy, especially in fragile patients. Disposable duodenoscopes seem to be the right tool to minimize the problem: a good choice for patients with many comorbidities or with a high risk of carrying multidrug resistant bacteria. Urgent endoscopy could also be a good setting for the use of single-use duodenoscopes, especially when the risk of the infection cannot be evaluated. Their safety and efficacy in performing ERCP has been proven in many studies. However, randomized clinical trials and comparative large studies with reusable scopes are lacking. Moreover, the present early stage of their introduction on the market does not allow a large economical evaluation for each health system. Thus, accurate economical and safety comparisons with cap-disposable duodenoscopes are needed. Moreover, the environmental impact of single-use duodenoscopes should be carefully evaluated, considering the ongoing climate change. In conclusion, definitive guidelines are needed to choose wisely the appropriate patients for ERCP with disposable duodenoscopes as the complete switch to single-use duodenoscopes seems to be difficult, to date. Many issues are still open, and they need to be carefully evaluated in further, larger studies. Full article

One of the most important health issues facing the world today is obesity. It is an important independent risk factor for developing type 2 diabetes. Harmine offers various pharmacological effects, such as anti-inflammatory and anti-tumor effects. The current study aims to investigate Harmine’s anti-diabetic and anti-adipogenic properties in albino mice after inducing low-grade inflammation with a high-fat diet (HFD). About forty-eight male albino mice were divided into four groups. Group 1: control mice were injected with daily saline and fed a normal chow diet of 21% protein for 5 months. Group 2: mice were treated daily with IP-injected Harmine (30 mg/kg body weight) and were fed a normal chow diet for 5 months. Group 3: mice were fed HFD to induce type 2 Diabetes Mellitus (T2DM) for 5 months. Group 4: mice were fed HFD for 14 weeks and treated with Harmine for the last 6 weeks. A figh-fat diet caused a significant increase in body and organ weight, lipid profiles, and destructive changes within the pancreas, kidney, and liver tissue. The administration of Harmine led to a remarkable improvement in the histological and ultrastructural changes induced by HFD. The findings indicate that mice cured using Harmine had lower oxidative stress, a higher total antioxidant capacity, and a reduced lipid profile compared to HFD mice. Harmine led to the hepatocytes partly restoring their ordinary configuration. Furthermore, it was noticed that the pathological incidence of damage in the structure of both the kidney and pancreas sections reduced in comparison with the diabetic group. Additional research will be required to fully understand Harmine and its preventive effects on the two forms of diabetes. Full article

Crohn’s disease (CD) is a chronic, relapsing disorder belonging to inflammatory bowel diseases (IBD). It is manifested by relapsing transmural inflammation found in any segment of the gastrointestinal tract. Chronic fatigue is a common and underrecognized symptom of CD for which the prevalence is much higher in the population of CD patients compared to the healthy population. It stems from an intricate web of interactions between various risk factors, and its pathophysiology is still not fully understood. The implementation of routine screening and a holistic, multidisciplinary approach involving psychological support may be crucial in the management of CD patients with chronic fatigue. There is currently no single intervention aimed at decreasing fatigue alone, and its treatment is especially difficult in patients with fatigue persisting despite clinical and endoscopic remission. Extensive research is still needed in order to be able to predict, prevent, identify, and ultimately treat fatigue associated with CD. The aim of this review is to summarize the knowledge on the etiology, diagnosis, and treatment of chronic fatigue in CD patients. Full article

MRE has become a standard imaging test for evaluating patients with small bowel pathology, but the indications, interpretation of imaging findings, methodology, and appropriate use must be standardized and widely known. Several signs of small bowel damage in inflammatory and non-inflammatory small bowel pathology include strictures, abscess, inflammatory activity, sinus tract, wall edema, fistula, mucosal lesions, and mesentery fat hypertrophy, all of which are widely and accurately explained by MRE. MRE is a non-invasive modality that accurately assesses the intra-luminal, parietal, and extra-luminal small bowel. The differential MRE appearance allows us to distinguish between different small bowel pathologies, such as neoplastic and non-neoplastic small bowel diseases. The purpose of this paper is to present the MRE technique, as well as the interpretation of imaging findings, through the approach of a rigorous stepwise methodology. Full article

In recent years, there has been a noteworthy revival of interest in the function of mast cells (MCs) in the human body. It is now acknowledged that MCs impact a wide array of processes beyond just allergies, leading to a shift in research direction. Unfortunately, some earlier conclusions were drawn from animal models with flawed designs, particularly centered around the receptor tyrosine kinase (Kit) pathway. Consequently, several subsequent findings may have been unreliable. Thus, what is now required is a re-examination of these earlier findings. Nevertheless, the remaining data are fascinating and hold promise for a better comprehension of numerous diseases and the development of more effective therapies. As the field continues to progress, many intriguing issues warrant further investigation and analysis. For instance, exploring the bidirectional action of MCs in rheumatoid arthritis, understanding the extent of MCs’ impact on symptoms associated with Ehlers–Danlos syndrome, and unraveling the exact role of the myofibroblast–mast cell–neuropeptides axis in the joint capsule during post-traumatic contractures are all captivating areas for exploration. Hence, in this review, we summarize current knowledge regarding the influence of MCs on the pathogenesis of selected musculoskeletal diseases, including rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, gout, muscle and joint injuries, tendinopathy, heterotopic ossification, and Ehlers–Danlos syndrome. We believe that this review will provide in-depth information that can guide and inspire further research in this area. Full article

Ovarian cancer (OC) is characterized by silent progression and late-stage diagnosis. It is critical to detect and accurately diagnose the disease early to improve survival rates. Tumor markers have emerged as valuable tools in the diagnosis and management of OC, offering non-invasive and cost-effective options for screening, monitoring, and prognosis. Purpose: This paper explores the diagnostic importance of various tumor markers including CA-125, CA15-3, CA 19-9, HE4,hCG, inhibin, AFP, and LDH, and their impact on disease monitoring and treatment response assessment. Methods: Article searches were performed on PubMed, Scopus, and Google Scholar. Keywords used for the searching process were “Ovarian cancer”, “Cancer biomarkers”, “Early detection”, “Cancer diagnosis”, “CA-125”,“CA 15-3”,“CA 19-9”, “HE4”,“hCG”, “inhibin”, “AFP”, “LDH”, and others. Results: HE4, when combined with CA-125, shows improved sensitivity and specificity, particularly in early-stage detection. Additionally, hCG holds promise as a prognostic marker, aiding treatment response prediction and outcome assessment. Novel markers like microRNAs, DNA methylation patterns, and circulating tumor cells offer potential for enhanced diagnostic accuracy and personalized management. Integrating these markers into a comprehensive panel may improve sensitivity and specificity in ovarian cancer diagnosis. However, careful interpretation of tumor marker results is necessary, considering factors such as age, menopausal status, and comorbidities. Further research is needed to validate and refine diagnostic algorithms, optimizing the clinical significance of tumor markers in ovarian cancer management. In conclusion, tumor markers such as CA-125, CA15-3, CA 19-9, HE4, and hCG provide valuable insights into ovarian cancer diagnosis, monitoring, and prognosis, with the potential to enhance early detection. Full article

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders, has proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured via passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured using ELISA kits, Western blotting, and immunostaining techniques. The data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p < 0.05~p < 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg, p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments and ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue. Considering the results obtained, DTZ might have a potential therapeutic role in treating and managing AD and related dementia pathologies due to its anti-dementia activity in SAD-type conditions in rats induced by ICV-STZ. Full article