Search Results (199)

Nutrition is being increasingly recognized as a modifiable adjuvant factor in symptom management, yet few studies have examined the direct contribution of fruit consumption to chronic disease outcomes. The existing research largely emphasizes broad dietary patterns or isolated nutrients, rather than specific fruit species and their complex bioactive profiles. This gap is particularly evident in conditions lacking disease-specific pharmacological treatments, such as fibromyalgia syndrome (FMS), where patients often depend on lifestyle adjustments and complementary strategies for symptom relief. The therapeutic use of fruits presents methodological challenges, as their biochemical composition is strongly influenced by abiotic and biotic stresses, seasonal and regional variations, as well as post-harvest handling and storage. Such variability complicates reproducibility and obscures causal links in clinical research. While reductionist approaches that isolate single compounds offer dose control, they risk losing synergistic effects inherent to whole fruits. Conversely, whole-fruit consumption preserves integrative complexity but introduces variability. Overcoming these limitations requires rigorous standardization across agricultural, nutritional, and clinical domains, accurate species and cultivar identification, controlled cultivation conditions, chemical fingerprinting, and biomarker validation. In this context, cacti fruits such as Opuntia ficus-indica (prickly pear), which is rich in betalains and polyphenols, emerge as promise adjuvant agents for FMS symptom management. We propose a protocol designed to systematically evaluate their efficacy and feasibility in clinical application, aiming to strengthen the reliability and accuracy of research outcomes. Full article

Chronic obstructive pulmonary disease (COPD) and insomnia are highly comorbid, yet their shared pathogenesis and therapeutic targets remain unclear. This study employed multidimensional approaches—including bidirectional Mendelian randomization (MR), transcriptomic analysis, weighted gene co-expression network analysis (WGCNA), and computational drug repositioning—to investigate causal relationships, shared pathways, and therapeutic strategies for COPD–insomnia comorbidity. MR analysis indicated that insomnia is a causal risk factor for COPD (OR = 2.04, 95% CI: 1.18–3.51; p = 0.011), with no reverse causality. Integrated transcriptomics of COPD (GSE148004) and insomnia (GSE208668) identified 230 co-dysregulated genes enriched in immune-inflammatory pathways (e.g., NF-κB signaling and cytokine response) and oxidative stress. Protein–protein interaction networks highlighted TNFAIP3 as a hub gene, confirmed by LASSO regression as a shared diagnostic biomarker. A co-expression network of 190 overlapping genes linked circadian disruption and airway inflammation. Drug repositioning nominated TNFAIP3-targeting agents, and molecular docking revealed high-affinity binding between berbamine and the TNFAIP3 OTU domain (ΔG = −9.25 kcal/mol). TNFAIP3 emerges as a dual regulator of inflammatory signaling and redox homeostasis. Our systems pharmacology approach bridges epidemiological causality and molecular mechanisms, supporting single-agent polypharmacology for COPD–insomnia comorbidity. Full article

Background: Insomnia is markedly more prevalent in rheumatoid arthritis (RA) patients than in the general population and is closely linked to pain, fatigue, psychological comorbidities, and systemic inflammation. Evidence suggests a bidirectional relationship, where active disease worsens sleep quality, while poor sleep amplifies inflammatory activity and symptom severity. Methods: A narrative review was conducted using PubMed, Scopus, Web of Science, and Embase to identify studies from the last 15 years involving adult RA patients. Inclusion criteria required assessment of insomnia or sleep quality in relation to disease activity, treatment outcomes, or inflammatory markers. Data from clinical trials, cohort studies, and reviews were synthesized to examine prevalence, mechanisms, and therapeutic implications. Results: Insomnia affects up to 45% of RA patients and correlates with higher DAS28 scores, elevated CRP/ESR, increased pain sensitivity, and reduced quality of life. Contributing factors include chronic pain, stiffness, elevated IL-6 and TNF-α, depression, anxiety, and medication side effects. Conventional DMARDs, corticosteroids, and biologics indirectly improve sleep via inflammation control, with IL-6 inhibition showing potential sleep-specific benefits. Psychotropic agents may help in comorbid depression/anxiety but are best combined with cognitive behavioral therapy for insomnia (CBT-I). Conclusions: Insomnia is a prevalent, multifactorial problem in RA that adversely affects disease activity, symptom burden, and functional outcomes. Integrating sleep evaluation into routine RA management and adopting interdisciplinary strategies that address both inflammation and sleep disturbance may enhance patient outcomes. High-quality longitudinal studies using objective sleep measures are needed to clarify causal relationships and optimize therapy. Full article

Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies. Full article

Tomato (Solanum lycopersicum L.) is among the most economically significant and nutritionally valuable vegetable crops grown globally. However, fungal diseases such as Early Blight caused by Alternaria alternata are a major factor limiting yield and fruit quality in tomato production. This study investigates the biocontrol potential of locally isolated rhizobacterium Pseudomonas yamanorum against A. alternata, the causal agent of early blight in tomato, under both in vitro and in planta conditions. In vitro assays demonstrated significant antifungal activity; in the dual confrontation assay, P. yamanorum (10⁸ CFU/mL) reduced A. alternata mycelial growth by 68.7%, while spore germination was inhibited by 88.7%. In planta trials demonstrated that plants treated with P. yamanorum (10⁷ CFU/mL) alone exhibited the lowest disease severity (2.5). The treatments also significantly enhanced plant growth, with shoot length reaching 45 cm versus 26 cm in infected controls. Biochemical analyses revealed increased catalase (94.84 units mg⁻¹ protein min⁻¹), peroxidase (5.83), and ascorbate peroxidase (67.01) activities in treated plants. Total polyphenol and protein contents also increased (0.81 mg/g and 15.82 mg/g, respectively). Furthermore, P. yamanorum treatments maintained fruit quality parameters such as firmness (3.13), sugar content (6.43 °Brix), and juice yield (55.88%), while reducing malondialdehyde (2.02 µmol/g Dry Weight) and electrical conductivity (0.59 mS/cm). These findings highlight P. yamanorum as a promising biocontrol agent and plant growth-promoting bacteria that improve disease resistance, which can be combined with salicylic acid to further enhance crop vigor and fruit quality under biotic stress. Full article

In recent years, symptoms of Twig Cankers and Shoot Blight (TCSB) have re-emerged in several Italian peach orchards, particularly within key production areas of the Emilia-Romagna region. The fungal pathogen Diaporthe amygdali is recognized as the primary causal agent of TCSB, leading to the rapid desiccation of shoots, flowers, leaves, and branches, often accompanied by resin exudation from cankers that appear in late winter or early spring. Given Italy’s position as the second-largest peach producer in Europe, ensuring sustainable yields and high fruit quality necessitates a deeper understanding of D. amygdali biology and the development of effective diagnostic and management tools. This study employed a hybrid whole-genome sequencing strategy, combining Illumina short-read and PacBio long-read technologies, to generate the first high-quality genome assembly of D. amygdali isolated from peach. The genome analysis revealed candidate virulence genes and other factors involved in pathogenicity, deepening our understanding of the infection strategies employed by D. amygdali. These findings may support the potential development of sustainable, effective strategies against TCSB, ultimately supporting resilient peach production in Italy and beyond. Full article

Parkinson’s disease (PD) is a progressive, irreversible neurodegenerative disorder characterized by motor impairments and a wide spectrum of non-motor symptoms, including gastrointestinal dysfunction, sleep disturbances, depression, and cognitive decline. These manifestations arise from disturbances across multiple systems—gastrointestinal, neuroendocrine, immune, enteric, and central nervous systems. Alterations in the gut microbiota may play a causal role in PD onset and frequently accompany disease progression. The gut–brain axis, particularly the vagus nerve, is increasingly recognized as a key communication pathway whose dysregulation contributes to systemic dysfunction and the breakdown of homeostasis, ultimately driving PD pathology. Currently, there is no cure for PD, and existing treatments primarily target symptom relief. Effective management of PD requires a comprehensive approach that integrates multiple pharmacologically active agents aimed at restoring impaired organ functions and, when possible, neutralizing toxic factors that accelerate disease progression. One promising therapeutic avenue lies in functional gut bacteria, which form the basis for developing live biotherapeutic products, postbiotics, and bacterial vesicles. In this review, we summarize current data on the effects of probiotics in PD, drawing on both animal models and clinical studies. We highlight the role of probiotics in modulating PD pathophysiology and discuss their potential as adjunctive therapeutic agents. To provide a broader perspective, we also include sections describing the clinical manifestations of PD, gut microbiota alterations associated with the disease, and the role of artificial intelligence, particularly machine learning, in constructing functional models of PD. Full article

Areca palm velarivirus 1 (APV1), the causal agent of yellow leaf disease (YLD), poses a serious threat to the economically important areca palm industry in the Hainan Province, China, yet its evolutionary dynamics remain poorly understood. Here, we performed a large-scale molecular survey by sequencing the coat protein (CP) gene from 364 APV1-infected samples collected across major cultivation regions of Hainan. Population genetic analyses revealed extremely high haplotype diversity (H_d = 0.997) but very low nucleotide diversity (π = 0.017). Neutrality tests (Tajima’s D = −2.266; Fu’s F_S = −23.697) and a unimodal mismatch distribution supported a scenario of recent demographic expansion from a restricted ancestral pool. Evolutionary analyses indicated that the CP gene is subject to strong purifying selection, although eight codons exhibited episodic positive selection, suggesting ongoing viral adaptation. Furthermore, we identified three distinct genetic clusters with significant geographic structuring, indicating that viral dissemination is shaped by local factors. Together, these results reveal a recent explosive invasion of APV1 characterized by rapid island-wide expansion and emerging local differentiation. This work provides novel insights into the evolutionary trajectory of APV1 and establishes a genomic basis for improved surveillance and management of YLD. Full article

‘Candidatus Phytoplasma solani’ is the causal agent of the Bois noir (BN), affecting grapevine worldwide. The complex epidemiology of BN, which involves multiple ‘Ca. P. solani’ host plants and insect vectors, as well as the occurrence of recovery (loss of symptoms on grapevine canopy), makes disease investigations and containment in vineyards difficult. To achieve early detection of ‘Ca. P. solani’, a droplet digital PCR (ddPCR)-based approach and quantitative (q)PCR assay were compared, testing specific primers based on the elongation factor Tu (tuf) gene using SYBR Green chemistry. The regression curve analysis of the ddPCR assay showed good linearity. Compared with the qPCR method, the sensitivity of ddPCR improved about 10-fold. The analysis of grapevine roots spiked with serial dilutions of ‘Ca P. solani’. PCR tuf fragments showed that qPCR was inhibited, while ddPCR was not affected. Testing 66 grapevine samples from 50 grapevine plants, the ddPCR provided superior diagnostic performance compared to qPCR in roots of symptomatic plants (75% detected by ddPCR, 41.6% by qPCR), roots of recovered plants (58.8% detected by ddPCR, 25% by qPCR), and asymptomatic leaf tissues from recovered plants (75% detected by ddPCR, 25% by qPCR). The ddPCR analysis allowed us to detect ‘Ca. P. solani’ on 40% of leaf samples from recovered plants and 20% of roots from asymptomatic plants. No differences among ddPCR and qPCR were found in detecting phytoplasma on symptomatic leaf samples. The ddPCR assay allowed the absolute quantification of ‘Ca. P. solani’ in complex matrices, such as roots, and when low titer of phytoplasma is present. Full article

Background: The United Arab Emirates (UAE) faces a high burden of type 2 diabetes mellitus (T2DM) and its complications. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiorenal benefits in clinical trials, real-world evidence on their association with calculated cardiovascular risk in Middle Eastern populations remains limited. This study evaluated the long-term real-world outcomes associated with SGLT2i use in Emirati patients with T2DM. Methods: We conducted a retrospective observational study of patients with T2DM initiated on SGLT2i (empagliflozin, dapagliflozin, or canagliflozin) at Tawam Hospital, UAE, between 1 January 2018 and 31 December 2018. Patients were followed for up to 5 years. Primary outcomes included changes in glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), and body mass index (BMI). A key secondary outcome was the change in 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the ACC/AHA Pooled Cohort Equations. Results: We included 185 patients (mean age 57 ± 12 years, 56.2% female), with 107 (57.8%) receiving empagliflozin, 54 (29.2%) dapagliflozin, 11 (5.9%) canagliflozin, and 13 (7.0%) who switched between agents. Significant improvements were observed in HbA1c (8.7 ± 1.8% to 8.2 ± 1.9%, p < 0.001), while eGFR showed preservation of renal function with an annual decline of 1.1 mL/min/1.73 m². Among 120 patients eligible for ASCVD risk assessment (excluding 65 with established cardiovascular disease), the mean 10-year ASCVD risk decreased from 22.3 ± 5.3% at baseline to 19.3 ± 4.9% at 5 years (absolute reduction −3.0%, 95% CI −2.4 to −3.6%, p < 0.001). Serious adverse events were rare, including acute kidney injury (1.1%) and fractures (1.6%). No episodes of diabetic ketoacidosis or severe hypoglycemia were observed. Conclusions: In this real-world cohort from the UAE, SGLT2 inhibitor use was associated with sustained glycemic control, preserved renal function, and lower calculated 10-year cardiovascular risk over 5 years. These observational findings, noted in the context of comprehensive risk factor management, support the potential benefits of SGLT2i in high-risk Middle Eastern patients with T2DM, though prospective controlled studies are needed to confirm causality. Full article

Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology. Full article

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Pinus massoniana Lamb. is an economically important conifer native to China. However, it is highly susceptible to the pine wood nematode (Bursaphelenchus xylophilus, PWN), the causal agent of pine wilt disease (PWD), resulting in substantial ecological and economic losses. To elucidate potential molecular defense mechanisms, 50 NAC (NAM, ATAF1/2, and CUC2) transcription factors (PmNACs) were identified in the P. massoniana genome. Phylogenetic analysis divided these PmNACs into seven subfamilies, and motif analysis identified ten conserved motifs associated with stress responses. Twenty-three genes were selected for expression analysis in various tissues and under exogenous salicylic acid (SA), methyl jasmonate (MeJA), and PWN infection. Six genes (PmNAC1, PmNAC8, PmNAC9, PmNAC17, PmNAC18, and PmNAC20) were significantly up-regulated by both hormonal treatment and PWN infection, implying their involvement in JA/SA-mediated immune pathways. Functional characterization showed PmNAC8 is a nuclear-localized transcription factor with autoactivation activity. Furthermore, transient overexpression of PmNAC8 in Nicotiana benthamiana induced reactive oxygen species (ROS) accumulation and necrotic lesions. Collectively, these results elucidate NAC-mediated defense responses to PWN infection in P. massoniana and identify candidate genes for developing PWD-resistant pine varieties. Full article

Evaluating risk in complex systems relies heavily on human auditors whose subjective assessments can be compromised by knowledge gaps and varying interpretations. This subjectivity often results in inconsistent risk evaluations, even among auditors examining identical systems, owing to differing pattern recognition processes. In this study, we propose a causality model that can improve the comprehension of risk levels by breaking down the risk factors and creating a layout of risk events and consequences in the system. To do so, the initial step is to define the risk event blocks, each comprising two distinct components: the agent and transfer mechanism. Next, we construct a causal map that outlines all risk event blocks and their logical connections, leading to the final consequential risk. Finally, we assess the overall risk based on the cause-and-effect structure. We conducted real-world illustrative examples comparing risk-level assessments with traditional experience-based auditor judgments to evaluate our proposed model. This new methodology offers several key benefits: it clarifies complex risk factors, reduces reliance on subjective judgment, and helps bridge the gap between subjective and objective uncertainty. The illustrative examples demonstrate the potential value of the model by revealing discrepancies in risk levels compared to traditional assessments. Full article

Exploring the action mechanisms and enhancement pathways of the resilience of agricultural product green supply chains is conducive to strengthening the system’s risk resistance capacity and providing decision support for achieving the “dual carbon” goals. Based on theories such as dynamic capability theory and complex adaptive systems, this paper constructs a resilience framework covering the three stages of “steady-state maintenance–dynamic adjustment–continuous evolution” from both single and multiple perspectives. Combined with 768 units of multi-agent questionnaire data, it adopts Structural Equation Modeling (SEM) and fuzzy-set Qualitative Comparative Analysis (fsQCA) to analyze the influencing factors of resilience and reveal the nonlinear mechanisms of resilience formation. Secondly, by integrating configurational analysis with machine learning, it innovatively constructs a resilience level prediction model based on fsQCA-XGBoost. The research findings are as follows: (1) fsQCA identifies a total of four high-resilience pathways, verifying the core proposition of “multiple conjunctural causality” in complex adaptive system theory; (2) compared with single algorithms such as Random Forest, Decision Tree, AdaBoost, ExtraTrees, and XGBoost, the fsQCA-XGBoost prediction method proposed in this paper achieves an optimization of 66% and over 150% in recall rate and positive sample identification, respectively. It reduces false negative risk omission by 50% and improves the ability to capture high-risk samples by three times, which verifies the feasibility and applicability of the fsQCA-XGBoost prediction method in the field of resilience prediction for agricultural product green supply chains. This research provides a risk prevention and control paradigm with both theoretical explanatory power and practical operability for agricultural product green supply chains, and promotes collaborative realization of the “carbon reduction–supply stability–efficiency improvement” goals, transforming them from policy vision to operational reality. Full article