Search Results (423)

Salinization of olive orchards constitutes a front-line agronomic challenge for farmers, consumers, and the scientific community as food security, olive logistics, and land use become more unsustainable and problematic. Plantlets of two olive varieties (var. Kalamon and var. Koroneiki) were tested for their performance under soil saline conditions, in which L-methionine, choline-Cl, and L-proline betaine were applied foliarly to alleviate adverse effects. The ‘Kalamon’ variety ameliorated its photosynthetic rates when L-proline betaine and L-methionine were administered at low saline exposure. The stressed varieties achieved higher leaf transpiration rates in the following treatment order: choline-Cl > L-methionine > L-proline betaine. Choline chloride supported stomatal conductance in stressed var. Kalamon olives without this pattern, which was also followed by var. Koroneiki. Supplementation regimes created a mosaic of responses on varietal water use efficiency under stress. The total phenolic content in leaves increased in both varieties after exogenous application only at the highest levels of saline stress. None of the substances applied to olive trees could stand alone as a tool to mitigate salinity stress in order to be recommended as a solid agronomic practice. The residual exploitation of amino acids by the olive orchard microbiome must also be considered as part of an environmentally friendly, integrated strategy to mitigate salinity stress. Full article

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite. Full article

Hemorrhoidal disease remains a prevalent yet often overlooked condition, affecting millions worldwide and imposing a substantial healthcare burden. Despite the availability of multiple treatment options, gaps persist in patient education, early symptom recognition, and optimal treatment selection. Recent advancements are evolving the pharmacist’s role in hemorrhoid management beyond traditional over-the-counter (OTC) and prescription approaches. The 2024 American Society of Colon and Rectal Surgeons (ASCRS) guidelines introduce updates on the use of phlebotonics, a class of venoactive drugs gaining recognition for their role in symptom management, yet largely underutilized in U.S. clinical practice. In parallel, novel clinical tools are reshaping how pharmacists engage in assessment and care. The integration of digital decision-support platforms and structured evaluation algorithms now empowers them to systematically evaluate symptoms, identify red flag signs, and optimize patient triage. These tools reduce diagnostic variability and improve decision-making accuracy. Given their accessibility and trusted role in frontline healthcare, pharmacists are well-positioned to bridge these critical gaps by adopting emerging treatment recommendations, leveraging algorithm-driven assessments, and reinforcing best practices in patient education and referral. This narrative review aims to equip pharmacists with updated insights into evidence-based hemorrhoid management strategies and provide them with structured assessment algorithms to standardize symptom evaluation and treatment pathways. By integrating these innovations, pharmacists can enhance treatment outcomes, promote patient safety, and contribute to improved quality of life (QoL) for individuals suffering from hemorrhoidal disease. Full article

Over the past two decades, the treatment landscape of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has undergone a profound transformation. Once considered the subtype with the worst prognosis, Ph+ ALL is now associated with the possibility of long-term survival in a significant proportion of patients. This dramatic improvement has been driven by the advent of tyrosine kinase inhibitors (TKIs) and, more recently, by the incorporation of blinatumomab, a bispecific T-cell engager antibody, into frontline therapeutic strategies. In this evolving context, two major areas have become the focus of clinical investigation: on the one hand, the identification of high-risk patients who truly benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT); on the other, the characterization of patients who can achieve durable responses without transplantation and who may be candidates for treatment discontinuation of TKIs. This review aims to summarize the current evidence supporting the concept of treatment-free remission (TFR) in Ph+ ALL. Full article

In hormone-dependent cancers, front-line treatment options include surgery and therapies that target hormone dependance. These therapies are effective initially but fail in tumors that recur, develop resistance or present at an advanced stage. Consequently, new therapeutic avenues are urgently needed. Increasing evidence implicates epigenetic modulators in tumor initiation, progression and therapeutic response, making them attractive biomarkers for patient stratification and targets for intervention. Over the past two decades, the discovery and development of small-molecule inhibitors directed against key epigenetic regulators have accelerated. This review provides a comprehensive overview of the major epigenetic targets, the inhibitors developed against them and the clinical trials currently underway in endocrine-related cancers. While epigenetic agents have shown limited benefits as monotherapies, their use in combination regimens is emerging as a strategy to overcome resistance and enhance the efficacy of existing treatments. We summarize the current landscape of combination trials, highlight early signs of clinical activity and discuss the opportunities and challenges inherent in integrating epigenetic drugs into the management of advanced endocrine-related cancers. Full article

Background: Colorectal cancer (CRC) is a prevalent global malignancy with particularly challenging treatment outcomes in advanced stages. Oxaliplatin (OXA) is a frontline chemotherapeutic agent for CRC. However, 15% to 50% of stage III patients experience recurrence due to drug resistance. Elucidating the molecular mechanisms underlying OXA resistance is, therefore, crucial for improving CRC prognosis. The role of DIRAS1, a RAS superfamily member with reported tumor-suppressive functions in various cancers, remains poorly defined in CRC. Methods: The effects of DIRAS1 on CRC cell proliferation and migration were evaluated using MTT, wound healing, and colony formation assays. Stable cell lines with knockdown or overexpression of DIRAS1 and PHB1 were established via plasmid and lentiviral systems. Drug sensitivity to OXA was assessed through cytotoxicity assays and IC₅₀ determination. Clinical relevance was validated through immunohistochemical analysis of CRC tissue samples. Transcriptomic sequencing was performed to explore downstream regulatory mechanisms. Results: DIRAS1 expression was positively correlated with OXA resistance and was significantly upregulated following prolonged chemotherapy exposure. Silencing DIRAS1 reduced the IC₅₀ of OXA in vitro and increased tumor sensitivity to OXA in vivo. Transcriptome analysis identified PHB1 as a downstream effector of DIRAS1. Functional studies revealed that PHB1 contributes to chemoresistance by maintaining mitochondrial stability. Conclusions: This study identifies DIRAS1 as a key contributor to OXA resistance in CRC by modulating PHB1 expression and mitochondrial function. Targeting the DIRAS1–PHB1 axis may offer a novel therapeutic strategy to overcome chemoresistance in CRC. Full article

The application of non-thermal (cold) plasmas is considered an environmentally friendly method that could affect plant metabolism and cellular development or can be used for the commercial production of natural products that cannot be chemically synthesized. In the present study, the non-embryogenic callus of iris (Iris reichenbachii Heuff.) was treated with a Radio Frequency (RF) plasma needle device using He as a working gas. We investigated short-term (up to seven days) and long-term (up to one year) changes on morphological, physiological and biochemical levels. An increased production of O₂⁻ and H₂O₂ was observed in the callus tissue after plasma treatment. The enzymes SOD and CAT represented the frontline in the antioxidant defense against reactive oxygen species (ROS) produced during the first hour of treatment, while POX was the leading antioxidant enzyme seven days after plasma treatment. Significant long-term morphological changes were observed in the calli due to the increased mitotic activity of the plant cells. In addition, three flavonoids (naringenin, apigenin and acacetin) and two isoflavonoids (irisolidone and irilone) were detected only in the plasma-treated tissue even one year after plasma treatment. The present study emphasizes the application of the plasma technique to promote meristematic activity and stimulate the production of specialized metabolites in iris calli. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Obesity and its related comorbidities continue to be a primary public health concern, especially in the United States (US). Such comorbidities include the top two causes of death in the US: cardiovascular disease and cancer. Obesity is also associated with several other chronic conditions that affect millions of adults and children, including diabetes, kidney, and liver disease. Weight loss has long been considered the front-line treatment and prevention strategy for these conditions. Lifestyle approaches, including dietary modification and increasing physical activity, are typically recommended for individuals with obesity, although rates of achieving and maintaining clinically meaningful weight loss remain low. Understanding the root causes of minimal weight loss and weight regain has been a prime focus among many researchers over the past several decades. The present review addresses several advantages of prioritizing exercise as an obesity and chronic disease treatment. We discuss current challenges when exercise is the primary treatment strategy, including physiological parameters that may influence the efficacy of exercise in addition to behavioral and environmental factors that play a role in exercise adherence and adoption. We also explore strategies and principles that, although not commonly utilized in an obesity/chronic disease treatment setting, may be applied and adapted to fit this model. Full article

Background/Objectives: Systemic sclerosis (SSc) is a progressive autoimmune disease characterized by widespread fibrosis, including skin thickening. Mycophenolate mofetil (MMF) is commonly used in SSc-associated interstitial lung disease, but its efficacy in improving skin fibrosis has not been systematically evaluated. This study aimed to assess the therapeutic effect of MMF on cutaneous sclerosis in SSc, as measured by the modified Rodnan skin score (mRSS). Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, Embase, and Web of Science were searched from January 2000 to March 2025. Studies reporting mRSS outcomes in SSc patients treated with MMF were included, provided that the effect of MMF could be separately evaluated when used alongside other therapies. Risk of bias was assessed using the Cochrane RoB 2.0 tool for randomized controlled trials and the ROBINS-I tool for non-randomized studies. A random-effects model was used to estimate the pooled mean change in mRSS. Heterogeneity and publication bias were evaluated. Results: Eight studies involving 569 patients were included. The pooled mean reduction in mRSS following MMF treatment was −5.82 (95% CI: −7.46 to −4.19), exceeding the minimal clinically important difference. Heterogeneity across studies was substantial (I² = 82.6%). A post hoc exploratory subgroup analysis suggested greater improvement in early disease (<2 years), though this finding requires confirmation in prospective studies. MMF was generally well tolerated, with low discontinuation rates due to adverse events. Conclusions: MMF is associated with a statistically and clinically significant improvement in skin fibrosis in patients with SSc. These findings support its use as a frontline therapy for progressive cutaneous involvement, although further prospective studies are needed to identify optimal candidates for treatment. Full article

Background/Objectives: Endometriosis, a chronic and debilitating gynecological disorder, exacts a heavy clinical and socioeconomic toll on women’s lives. Despite its prevalence, its timely diagnosis and effective management are hindered by pervasive knowledge gaps among frontline nursing professionals, and these are especially pronounced in under-researched regions such as Al-Jouf, Saudi Arabia. Aim: Guided by the Knowledge–Attitude–Practice model, this study aimed to assess the level of endometriosis-related knowledge among nurses in the Al-Jouf region of Saudi Arabia and to identify the sociodemographic and professional determinants of knowledge levels. Methods: A cross-sectional, descriptive-analytical design was employed between January and July 2024, enrolling 215 nurses from a principal maternity and children’s hospital and two primary healthcare centers in Sakaka. A rigorously validated, bilingual 20-item questionnaire assessing four domains (definition, risk factors, clinical manifestations, and treatment goals) was administered. Data were analyzed using descriptive statistics, multiple linear regression, and binary logistic regression to elucidate predictors of knowledge. Results: A concerning picture emerged: 61% of participants scored below 60% (indicative of low knowledge), with only 6% achieving high scores. Higher educational attainment proved the strongest predictor (β = 0.415, p < 0.001), followed by age (β = 0.232, p < 0.001), years of experience (β = 0.149, p = 0.041), and direct patient care exposure (β = 0.168, p = 0.021). Collectively, these factors explained 37.6% of the variance in knowledge scores, underscoring a critical deficit in endometriosis management preparedness. Conclusions: The stark deficiencies in endometriosis knowledge among nurses in Al-Jouf call for immediate, tailored educational and policy interventions. Strengthening clinical competencies is essential for fostering early diagnosis and improving care outcomes for women burdened by this complex condition. Full article

In recent years, global public health security has encountered significant challenges, with infectious diseases accounting for approximately 25% of global mortality annually. The worldwide pandemic instigated by the novel coronavirus, alongside the persistent threats posed by Ebola, influenza, and multidrug-resistant bacteria, has severely compromised human health, economic development, and social stability. Within this context, the development of rapid and precise pathogen detection technologies has emerged as a critical frontline defense for epidemic prevention and control, serving as a pivotal component in the implementation of the “early detection, early isolation, and early treatment” strategy. The Argonaute (Ago) protein, recognized as a programmable and target-specific activated nuclease, has demonstrated substantial potential in the realm of nucleic acid detection due to its distinctive biological properties, garnering considerable attention. In this study, we delineate the structural characteristics of Ago proteins and elucidate the mechanism underlying their nuclease activity. Furthermore, we review the principles of nucleic acid detection based on Argonaute and provide a comprehensive analysis of recent advancements in related detection systems. Additionally, we compare the advantages of detection based on Argonaute with other detection methodologies. Through a comprehensive analysis, we aim to provide a robust theoretical foundation and an advanced technical reference for the development of new-generation nucleic acid detection platforms with high sensitivity and high specificity. Full article

Radical chemoradiotherapy has been used as a frontline treatment for squamous cell cancer of the anus for the last 30–40 years. Considerable acute and chronic adverse effects have been observed following radiotherapy using 2D and 3D techniques. A case of very late-onset severe chronic toxicity in a patient 26 years after radiotherapy is presented. The patient underwent radical chemoradiotherapy for squamous anal cancer stage T3N3M0 in 1998. In the anal region, cumulative doses up to 77.6 Gy (including electron boost) were administered. Durable complete regression of the disease was achieved. Fourteen years after treatment, the patient developed vast fibroatrophy of the anus and perineum, progressing within the subsequent four years to necrosis and sphincter loss. Twenty years after treatment, the asymptomatic osteonecrotic foci in the left femur appeared on MRI scans. Despite two courses of hyperbaric oxygen treatment, the fibroatrophy and subsequent necrosis of soft tissues remained progressive, but the osteonecrosis was stable. Twenty-six years after treatment, the progressive changes induced symptomatic osteomyelitis of the ischium and pubic bone. The patient now requires permanent supportive treatment. The presented case is exceptional in the very late-onset typical chronic adverse effects developing after non-conformal radiotherapy administered at high doses as part of contemporary treatment protocols. There is little evidence regarding the late onset of chronic adverse effects, since the follow-up period is usually shorter than that of the case presented. Moreover, a significant portion of patients do not survive to reach the late-onset period of adverse effects. The presented case shows that there may be long-term survivors of anal cancer in the population who were treated with outdated techniques and who still carry a risk of late-onset severe, progressive adverse effects. Full article

Background/Objectives: Imatinib, a first-generation tyrosine kinase inhibitor, is the standard treatment for chronic myeloid leukemia (CML). Although generic formulations have improved access, concerns regarding their efficacy and safety remain. This study aimed to compare the clinical outcomes and adverse events of original and generic imatinib in patients with CML in Thailand. Methods: We conducted a retrospective cohort study of patients with chronic-phase CML receiving frontline imatinib at Chiang Mai University Hospital between January 2012 and September 2022. Treatment responses, event-free survival (EFS), overall survival (OS), and adverse events were also analyzed. Results: Among the 71 patients, 46 (64.8%) received original imatinib, and 25 (35.2%) received generic imatinib. The median follow-up period was 80.3 months (IQR: 52.0–106.4). At 12 months, there were no significant differences in the cumulative complete cytogenetic response (73.3% vs. 70.8%, p = 0.825) or major molecular response (35.6% vs. 41.7%, p = 0.618). Although EFS was not significantly different between the groups, OS was significantly longer in patients receiving original imatinib (p < 0.001). Conclusions: Although early treatment responses and EFS were similar, generic imatinib was associated with an inferior OS. These findings highlight the need for close monitoring and further evaluation of long-term outcomes when using generic formulations. Full article