Circulating tumor cells clusters and their role in Breast cancer metastasis; a review of literature.

Breast cancer is a significant and deadly threat to women globally. Moreover, Breast cancer metastasis is a complicated process involving multiple biological stages, which is considered a substantial cause of death, where cancer cells spread from the original tumor to other organs in the body-representing the primary mortality factor. Circulating tumor cells (CTCs) are cancer cells detached from the primary or metastatic tumor and enter the bloodstream, allowing them to establish new metastatic sites. CTCs can travel alone or in groups called CTC clusters. Studies have shown that CTC clusters have more potential for metastasis and a poorer prognosis than individual CTCs in breast cancer patients. However, our understanding of CTC clusters' formation, structure, function, and detection is still limited. This review summarizes the current knowledge of CTC clusters' biological properties, isolation, and prognostic significance in breast cancer. It also highlights the challenges and future directions for research and clinical application of CTC clusters.

Throat spray formulated with virucidal Pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS CoV-2.

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would maximize the antiviral activity of the throat spray. Two self-nanoemulsifying formulas that were diluted with different vehicles to prepare eight CUR-loaded SNESNS (self-nanoemulsifying self-nanosuspension) formulas. In vitro characterization studies and in vitro anti-SARS-CoV-2 effect revealed that the optimal formula, consisted of 20 % Anise oil, 70 % Tween 80, 10 % PEG 400, and 0.1 %w/w CUR, diluted with DEAE-Dx. Preclinical toxicity tests on male rats confirmed the safety of a mild throat spray dose (5 µg/mL CUR). In a rat model of acute pharyngitis induced by ammonia, post-treatment with the optimal formula of CUR loaded SNESNS for one week significantly reduced elevated proinflammatory markers (TNF-α, IL6, MCP1, and IL8). In conclusion, our CUR-loaded SNESNS formula, at 5 µg/mL concentration, shows promising effect as a prophylactic throat spray against SARS-CoV-2 and as a treatment for pharyngitis.

Ticagrelor Versus Clopidogrel in Acute Large-Vessel Ischemic Stroke: A Randomized Controlled Single-Blinded Trial.

BACKGROUND: Large-vessel ischemic stroke represents about 25-40% of all ischemic strokes. Few clinical trials compared ticagrelor versus clopidogrel in ischemic stroke patients; all these studies included only patients with a transient ischemic attack or minor stroke; moreover, none of these studies included patients from North Africa. OBJECTIVES: We aimed to compare ticagrelor versus clopidogrel in the first-ever large-vessel occlusion (LVO) acute ischemic stroke in Egypt. METHODS: Our trial involved 580 first-ever LVO ischemic stroke patients who were randomly assigned to administer loading and maintenance doses of ticagrelor or clopidogrel. Screening, randomization, and start of treatment occurred during the first 24 hours of the stroke. RESULTS: 580 patients were included in the intention-to-treat analysis. Thirty patients in the ticagrelor group and 49 patients in the clopidogrel group experienced a new ischemic or hemorrhagic stroke at 90 days (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.38-0.98; p-value = 0.04), 36 patients in the ticagrelor group, and 57 in the clopidogrel group experienced composite of a new stroke, myocardial infarction, or death due to vascular insults (HR 0.56; 95% CI 0.37-0.87; p = 0.009). Patients who received ticagrelor had better clinical outcomes regarding National Institutes of Health Stroke Scale (NIHSS) reduction and a favorable modified Rankin scale (mRS) score. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. CONCLUSION: Patients with acute large-vessel ischemic stroke who received ticagrelor within the first 24 hours after ischemic stroke had better clinical outcomes based on recurrent stroke rates, NIHSS reduction, and favorable mRS rates compared with those who received clopidogrel. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. TRIAL REGISTRATION: Clinical trials.gov (NCT06120725).

New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Multisite Pain and Intensity were Associated with History Fall among Older Adults: A Cross-Sectional Study.

Purpose: This study examined the independent associations among multisite pain, pain intensity, and the risk of falls, including a history of falls in the previous 12 months and frequent falls (≥ two falls vs one or two falls) among community-dwelling older adults. Methods: A cross-sectional design from Wave 2 of the National Social Life, Health, and Aging Project was used. Data on pain intensity and location (45 sites) over the past 4 weeks were collected. Multisite pain was categorized into four groups: none, one, two, and three or more sites. The main outcomes of falls were a history of falls and frequent falls. The covariates included age, sex, race, body mass index, education, medications, and comorbidities. Results: Among 3,196 participants in Wave 2, 2,697 were included because of missing key variables related to pain and fall history. The prevalence of falls and frequent falls were 30.3% (n = 817) and 12.6% (n = 339), respectively. Multisite pain at ≥ three sites (odds ratio (OR) 2.04, confidence interval (CI) [1.62, 2.57]; p < 0.001) and two sites (OR 1.72, 95% CI [1.30, 2.27]; p < 0.001) was significantly associated with an increased risk of falls. An increase in pain intensity was significantly associated with an increased risk of fall (OR 1.28, 95% CI [1.15, 1.44], p < 0.001), independent of multisite pain. Multisite pain at ≥3 sites (OR 2.19, 95% CI [1.56, 3.07], p < 0.001) and 2 sites (OR 1.54, 95% CI [1.01, 2.34], p = 0.045) was associated with an increased risk of frequent falls. An increase in pain intensity was associated with risk of frequent falls (OR 1.64, 95% CI [1.40, 1.91], p < 0.001), independent of multisite pain. Conclusion: Multisite pain and pain intensity were associated with a history of falls and frequent falls among older adults, emphasizing the need for routine pain evaluation to develop fall prevention strategies in this population.

Modified gastro-soleus turn-down flap for chronic or neglected achilles tendon ruptures.

BACKGROUND: Achilles' tendon chronic rupture is a common entity that is usually misdiagnosed or mistreated. Hence, she was presented to us later or with complications affecting her gait. Surgical resection is needed to either bridge the gap or reinforce the strength of the tendon repair. OBJECTIVES: Our study's goal was to assess the clinical results of repairing chronic Achilles' tendon lesions employing the middle segment of the proximal portion of the tendon (gastro-soleus), as a turn-down flap. METHODS: Our prospective interventional single arm study included 18 patients with chronic Achilles' tendon rupture attending at Al-Azhar university hospitals in Cairo, Egypt from May 2020 to April 2023. Diagnosis of the patients was confirmed by radiographic and clinical investigations. They were all treated with the same open reconstruction procedure using a modified GSF. The average follow-up was 12 months. The results of this study were assessed by the Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) score, and capacity to perform repeated heel raises on the affected side. RESULTS: The mean operative time was 72.77 min. The median (IQR) time of reconstruction was 10 (8-12) after the injury. The median (IQR) length of flab was 4.5 (4.3-5) 9 (Table 2). No intraoperative complications occurred. The typical follow-up period was 12 months (6-18 months). In terms of the ATRS, we found a significant reduction from 82.8 ± 3 preoperatively to 20.8 ± 6.7 at 12 months postoperatively (P value = 0.001). As regards the AOFAS score, it was increased from 49.5 ± 10 preoperatively to 83.8 ± 8.5 12 months postoperatively (P = 0.001). In terms of the post operative complications, there was no re-rupture. Two patients experienced superficial wound infection which improved with daily dressing and antibiotics. Additionally, two patients had slight ankle stiffness four months after the operation, which improved after programmed rehabilitation at the sixth month. CONCLUSION: The modified GSTF is a simple, safe, well-tolerated and effective method of treatment with excellent functional results and greater patient content.

Molybdenum inhibited the growth of Phytophthora nicotiana and improved the resistance of Nicotiana tabacum L. against tobacco black shank.

Tobacco black shank (TBS) is a soil-borne fungal disease caused by Phytophthora nicotiana (P. nicotianae), significantly impeding the production of high-quality tobacco. Molybdenum (Mo), a crucial trace element for both plants and animals, plays a vital role in promoting plant growth, enhancing photosynthesis, bolstering antioxidant capacity, and maintaining ultrastructural integrity. However, the positive effect of Mo on plant biotic stress is little understood. This study delves into the inhibitory effects of Mo on P. nicotianae and seeks to unravel the underlying mechanisms. The results showed that 16.32 mg/L of Mo significantly inhibited mycelial growth, altered mycelial morphological structure, damaged mycelial cell membrane, and ultimately led to the leakage of cell inclusions. In addition, 0.6 mg/kg Mo applied in soil significantly reduced the severity of TBS. Mo increased photosynthetic parameters and photosynthetic pigment contents of tobacco leaves, upregulated expression of NtPAL and NtPPO resistance genes, as well as improved activities of SOD, POD, CAT, PPO, and PAL in tobacco plants. Furthermore, Mo could regulate nitrogen metabolism and amino acids metabolism to protect tobacco plants against P. nicotianae infection. These findings not only present an ecologically sound approach to control TBS but also contribute valuable insights to the broader exploration of the role of microelements in plant disease management.

An LIR motif in the Rift Valley fever virus NSs protein is critical for the interaction with LC3 family members and inhibition of autophagy.

Rift Valley fever virus (RVFV) is a viral zoonosis that causes severe disease in ruminants and humans. The nonstructural small (NSs) protein is the primary virulence factor of RVFV that suppresses the host's antiviral innate immune response. Bioinformatic analysis and AlphaFold structural modeling identified four putative LC3-interacting regions (LIR) motifs (NSs 1-4) in the RVFV NSs protein, which suggest that NSs interacts with the host LC3-family proteins. Using, isothermal titration calorimetry, X-ray crystallography, co-immunoprecipitation, and co-localization experiments, the C-terminal LIR motif (NSs4) was confirmed to interact with all six human LC3 proteins. Phenylalanine at position 261 (F261) within NSs4 was found to be critical for the interaction of NSs with LC3, retention of LC3 in the nucleus, as well as the inhibition of autophagy in RVFV infected cells. These results provide mechanistic insights into the ability of RVFV to overcome antiviral autophagy through the interaction of NSs with LC3 proteins.

Monitoring coeliac disease in 2024, time to change practice?

PURPOSE OF REVIEW: Persistent villous atrophy is associated with morbidity in coeliac disease and most commonly due to ongoing gluten ingestion. Current methods for assessing gluten exposure and persisting villous atrophy include dietary questionnaires and repeat duodenal biopsy, which have limited accuracy or are invasive. This review discusses adjunctive and/or novel tests that could be used to overcome these challenges. RECENT FINDINGS: Small bowel capsule endoscopy is well tolerated and helps to evaluate for persisting villous atrophy and importantly, complications associated with coeliac disease. Testing for urinary and/or stool gluten immunogenic peptides may help identify recent gluten exposure, but further studies are still warranted to evaluate the accuracy and applicability of this approach. Measuring spikes in circulating Interleukin-2 following gluten challenge has shown promise for coeliac disease diagnosis, and thus may serve as a useful confirmatory test in those with persisting symptoms but provides no information on mucosal inflammation. No specific gut microbial signature has been identified in coeliac disease; however, studies have shown a reduced microbial diversity in active disease, which with future refinement may prove clinically useful. SUMMARY: There is no evidence to support alternative methods for assessing persisting villous atrophy in coeliac disease over performing an up-to-date duodenal biopsy. Monitoring for adherence to a gluten-free diet remains clinically challenging and should be a priority for future research.

Predictors of the unfavorable outcomes in acute ischemic stroke patients treated with alteplase, a multi-center randomized trial.

Worldwide, stroke is a leading cause of long-term disability in adults. Alteplase is the only approved treatment for acute ischemic stroke (AIS) and results in an improvement in a third of treated patients. We evaluated the post-stroke unfavourable outcome predictors in alteplase-treated patients from Egypt and Saudi Arabia. We assessed the effect of different risk factors on AIS outcomes after alteplase in Egypt and Saudi Arabia. Our study included 592 AIS alteplase-treated patients. The relationship between risk factors, clinical presentation, and imaging features was evaluated to predict factors associated with poor outcomes. An mRS score of three or more was used to define poor outcomes. Poor outcome was seen in 136 patients (23%), and Patients with unfavourable effects had significantly higher admission hyperglycaemia, a higher percentage of diabetes mellitus, cardioembolic stroke, and a lower percentage of small vessel stroke. Patients with higher baseline NIHSS score (OR 1.39; 95% CI 1.12-1.71; P = 0.003), admission hyperglycaemia (OR 13.12; 95% CI 3.37-51.1; P < 0.001), and post-alteplase intracerebral haemorrhage (OR 7.41; 95% CI 1.69-32.43; P = 0.008) independently predicted unfavourable outcomes at three months. In AIS patients treated with alteplase, similar to reports from other regions, in patients from Egypt and Saudi Arabia also reveal that higher NIHSS, higher serum blood sugar, and post-alteplase intracerebral haemorrhage were the predictors of unfavourable outcomes three months after ischemic stroke.Trial registration: (clinicaltrials.gov NCT06058884), retrospectively registered on 28/09/2023.

Locustamigratoria (L.) (Orthoptera) in a warming world: unravelling the ecological consequences of climate change using GIS.

The migratory locust, Locustamigratoria (L.), a significant grasshopper species known for its ability to form large swarms and cause extensive damage to crops and vegetation, is subject to the influence of climate change. This research paper employs geographic information system (GIS) and MaxEnt ecological modelling techniques to assess the impact of climate change on the distribution patterns of L.migratoria. Occurrence data and environmental variables are collected and analysed to create predictive models for the current and future distribution of the species. The study highlights the crucial role of climate factors, particularly temperature and precipitation, in determining the locust's distribution. The MaxEnt models exhibit high-performance indicators, accurately predicting the potential habitat suitability of L.migratoria. Additionally, specific bioclimatic variables, such as mean temperature and annual precipitation, are identified as significant factors influencing the species' presence. The generated future maps indicate how this species will invade new regions especially in Europe. Such results predict the risk of this destructive species for many agriculture communities as a direct result of a warming world. The research provides valuable insights into the complex relationship between locust distribution and environmental factors, enabling the development of effective strategies for locust management and early warning systems to mitigate the impact on agriculture and ecosystems.

The effect of lacosamide on calcitonin gene-related peptide serum level in episodic migraine patients: a randomized, controlled trial.

BACKGROUND: Migraine affects 11-15% of people worldwide, and the calcitonin gene-related peptide (CGRP) is released during the migraine attack, producing pulsating pain of migraine. Also, lacosamide reacts with collapsin-response mediator protein 2, preventing its phosphorylation and leading to the inhibition of CGRP release in the trigeminal system. OBJECTIVE: The primary outcome was the difference in the serum level of CGRP-LI after three months of treatment with either lacosamide and ibuprofen or ibuprofen alone in episodic migraine patients. The secondary outcomes were assessing safety and efficacy of lacosamide in episodic migraine patients. METHODS: We conducted an open-label randomized controlled trial on episodic migraine patients aged 10-55 years diagnosed according to (ICHD-3) in Kafr El-Sheikh University Hospital, Egypt. We assessed serum levels of CGRP-LI before and three months after treatment in our two groups, the lacosamide, and the control groups. We also assessed the side effects of treatment in each group, the percentage of patients who achieved ≥ 50% reduction in the migraine monthly days (MMD) frequency and the percentage of patients who achieved pain freedom within 2 h in ≥ 4 of 5 attacks in each group. RESULTS: 200 episodic migraine patients completed the study. There was a statistically significantly higher reduction in the serum CGRP-LI level in the lacosamide group compared with the control group. In addition, lacosamide was well tolerated by patients. Also, the lacosamide group had statistically significant higher percentage of patients who achieved ≥ 50% reduction in the migraine monthly days (MMD) frequency and pain freedom within two hours in ≥ 4 of 5 attacks with P-values 0.002, 0.02 respectively. CONCLUSION: The daily use of lacosamide 50 mg Bid for three months in episodic migraine patients was associated with a significant reduction in serum CGRP-LI, better clinical outcomes regarding frequency and duration of migraine attacks, and was well tolerated by patients. These results were derived from an open-label pilot study that needed to be thoroughly investigated by a large-scale, randomized, double-blinded, placebo-controlled study. TRIAL REGISTRATION:  We registered our trial on ClinicalTrials.gov, named after "The Lacosamide's Effect on Calcitonin Gene-related Peptide in Migraine Patients," and with a clinical trial number (NCT05632133)-August 8, 2023.

Targeting the PI3K/pAKT/mTOR/NF-κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk.

Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep-G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF-κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p-AKT, PI3K, mTOR, NF-κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF-κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.

Examining the Effects of Asiaticoside on Dental Pulp Stem Cell Viability and Proliferation: A Promising Approach to Root Canal Treatment.

AIM: This study aims to evaluate the impact of asiaticoside (AC) on the viability and proliferation of dental pulp stem cells (DPSCs), considering the known negative effects of routinely used intracanal medicaments. This evaluation will be compared with the outcomes from using traditional intracanal medicaments, specifically triple antibiotic paste (TAP) and calcium hydroxide [Ca(OH)2]. MATERIALS AND METHODS: The DPSCs were obtained from the third molars of an adult donor. The application of flow cytometry was employed to do a phenotypic analysis on DPSCs using CD90, CD73, CD105, CD34, CD14, and CD45 antibodies. The methylthiazol tetrazolium (MTT) assay was employed to assess cellular viability. The cells were treated with different concentrations of TAP and Ca(OH)2 (5, 2.5, 1, 0.5, and 0.25 mg/mL), along with AC (100, 50, 25, 12.5, and 6.25 µM). A cell proliferation rate was performed at 3, 5, and 7 days. RESULTS: The characterization of DPSCs was conducted by flow cytometry analysis, which verified the presence of mesenchymal cell surface antigen molecules (CD105, CD73, and CD90) and demonstrated the absence of hematopoietic markers (CD34, CD45, and CD14). Cells treated with concentrations over 0.5 mg/mL of TAP and Ca(OH)2 showed a notable reduction in cell viability in comparison to the untreated cells (p < 0.05). Additionally, the cells treated with different concentrations of AC 12.5, 6.25, 25, and 50 µM did not differ significantly from the untreated cells (p > 0.05). Nevertheless, cells treated with concentrations of 100 µM showed a significant reduction in viability compared to the untreated cells (p < 0.05). After a period of 7 days, it was noted that cells exposed to three different concentrations of AC (50, 25, and 12.5 µM) had a notable rise in cell density in comparison to TAP and Ca(OH)2 (p < 0.05). Furthermore, cells that were exposed to a concentration of 12.5 µM exhibited the highest cell density. CONCLUSION: The cellular viability of the AC-treated cells was superior to that of the TAP and Ca(OH)2-treated cells. Moreover, the AC with a concentration of 12.5 µM had the highest degree of proliferation. CLINICAL SIGNIFICANCE: This study underscores the importance of evaluating alternative root canal medicaments and their effects on DPSCs' growth and vitality. The findings on AC, particularly its influence on the survival and proliferation of DPSCs, offer valuable insights for its probable use as an intracanal medication. This research contributes to the ongoing efforts to identify safer and more effective intracanal treatments, which are crucial for enhancing patient outcomes in endodontic procedures. How to cite this article: Alazemi MJ, Badawi MF, Elbeltagy MG, et al. Examining the Effects of Asiaticoside on Dental Pulp Stem Cell Viability and Proliferation: A Promising Approach to Root Canal Treatment. J Contemp Dent Pract 2024;25(2):118-127.

Climate changes altered the citrus fruit quality: A 9-year case study in China.

Global climate change has significantly impacted the production of various crops, particularly long-term fruit-bearing plants such as citrus. This study analyzed the fruit quality of 12 citrus orchards (Citrus Sinensis L.Osbeck cv. Bingtang) in a subtropical region in Yunnan, China from 2014 to 2022. The results indicated that high rainfall (>220 mm) and low cumulative temperature (<3150 °C) promoted increases in titratable acidity (>1.8 %) in young fruits. As the fruits further expanded (with a horizontal diameter increasing from 50 to 65 mm), excessive rainfall (300-400 mm), lower cumulative temperature (<2400 °C), and a reduced diurnal temperature range (<10 °C) hindered decreases in titratable acidity. Conversely, low rainfall (<220 mm), high cumulative temperature (>3150 °C), and a high diurnal temperature range (>14 °C) promoted the accumulation of soluble solids in young fruits (9 %) at 120 days after flowering (DAF). Furthermore, low rainfall (<100 mm) favored the accumulation of soluble solids (1.5 %) during fruit expansion (195-225DAF). To quantify the relationship between fruit acidity and climate variables at 120 DAF, we developed a regression model, which was further validated by actual measurements and accurately predicted fruit acidity in 2023. Our findings have the potential to assist citrus growers in optimizing cultivation techniques for the production of high-quality citrus under increasingly variable climatic conditions.

Macrophage polarization in lymph node granulomas from cattle and pigs naturally infected with Mycobacterium tuberculosis complex.

Tuberculosis in animals is caused by members of the Mycobacterium tuberculosis complex (MTC), with the tuberculous granuloma being the main characteristic lesion. The macrophage is the main cell type involved in the development of the granuloma and presents a wide plasticity ranging from polarization to classically activated or pro-inflammatory macrophages (M1) or to alternatively activated or anti-inflammatory macrophages (M2). Thus, this study aimed to analyze macrophage polarization in granulomas from cattle and pig lymph nodes naturally infected with MTC. Tuberculous granulomas were microscopically categorized into four stages and a panel of myeloid cells (CD172a/calprotectin), M1 macrophage polarization (iNOS/CD68/CD107a), and M2 macrophage polarization (Arg1/CD163) markers were analyzed by immunohistochemistry. CD172a and calprotectin followed the same kinetics, having greater expression in late-stage granulomas in pigs. iNOS and CD68 had higher expression in cattle compared with pigs, and the expression was higher in early-stage granulomas. CD107a immunolabeling was only observed in porcine granulomas, with a higher expression in stage I granulomas. Arg1+ cells were significantly higher in pigs than in cattle, particularly in late-stage granulomas. Quantitative analysis of CD163+ cells showed similar kinetics in both species with a consistent frequency of immunolabeled cells throughout the different stages of the granuloma. Our results indicate that M1 macrophage polarization prevails in cattle during early-stage granulomas (stages I and II), whereas M2 phenotype is observed in later stages. Contrary, and mainly due to the expression of Arg1, M2 macrophage polarization is predominant in pigs in all granuloma stages.

Facile and Novel Synthetic Approach, Molecular Docking, Molecular Dynamics, and Drug-Likeness Evaluation of 9-Substituted Acridine Derivatives as Dual Anticancer and Antimicrobial Agents.

In the present study, numerous acridine derivatives A1-A20 were synthesized via aromatic nucleophilic substitution (SNAr) reaction of 9-chloroacridine with carbonyl hydrazides, amines, or phenolic derivatives depending upon facile, novel, and eco-friendly approaches (Microwave and ultrasonication assisted synthesis). The structures of the new compounds were elucidated using spectroscopic methods. The title products were assessed for their antimicrobial, antioxidant, and antiproliferative activities using numerous assays. Promisingly, the investigated compounds mainstream revealed promising antibacterial and anticancer activities. Thereafter, the investigated compounds' expected mode of action was debated by using an array of in silico studies. Compounds A2 and A3 were the most promising antimicrobial agents, while compounds A2, A5, and A7 revealed the most cytotoxic activities. Accordingly, RMSD, RMSF, Rg, and SASA analyses of compounds A2 and A3 were performed, and MMPBSA was calculated. Lastly, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses of the novel acridine derivatives were investigated. The tested compounds' existing screening results afford an inspiring basis leading to developing new compelling antimicrobial and anticancer agents based on the acridine scaffold.

Cost-benefits and environmental impact of the no-biopsy approach for the diagnosis of coeliac disease in adults.

Objective: Recent evidence suggests that adult patients with IgA tissue transglutaminase levels of ≥10× the upper limit of normal could be accurately diagnosed with coeliac disease without undergoing endoscopy and biopsy. We aimed to evaluate the cost-benefits and the environmental impact of implementing the no-biopsy approach for diagnosing coeliac disease in clinical practice. Design: We calculated the overall direct and indirect costs of the conventional serology-biopsy approach and the no-biopsy approach for the diagnosis of coeliac disease based on the national average unit costs and the Office of National Statistics data. We further estimated the environmental impact of avoiding endoscopy based on the estimated greenhouse gas emissions from endoscopy. Results: Approximately 3000 endoscopies for suspected coeliac disease could be avoided each year in the UK. Implementing the no-biopsy approach for the diagnosis of coeliac disease in adults could save the National Health Service over £2.5 million in direct and indirect costs per annum and reduce endoscopy carbon footprint by 87 tonnes of CO2 per year, equivalent to greenhouse gas emissions from driving 222 875 miles, carbon emissions from charging over 10 million smartphones and the carbon sequestrated by 1438 trees grown for 10 years. Conclusion: The implementation of this non-invasive green approach could be an essential first step in the 'Reduce' strategy advocated by the British Society of Gastroenterology and other international endoscopy societies for sustainable endoscopy practice.

The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis.

BACKGROUND: Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to each case. This study aimed to evaluate the therapeutic effects of topical application of miconazole and miconazole-loaded chitosan nanoparticles in treatment of diabetic patients with oral candidiasis. METHODS: In this randomized controlled clinical trial. A total of 80 diabetic patients presenting with symptomatic oral candidiasis were randomly assigned into two treatment groups: miconazole and miconazole-loaded chitosan nanoparticles. The patients were treated for 28 days, and clinical assessments were conducted at baseline, 7, 14, 21 and 28 days. Clinical parameters, including signs and symptoms of oral candidiasis were evaluated and microbiological analysis was performed to determine the Candida species and assess their susceptibility to the antifungal agents. Statistical analysis was done to the categorical and numerical data using chi-square test and Kruskal Wallis test. RESULTS: The antifungal efficacy between the miconazole and miconazole-loaded chitosan nanoparticles (CS-MCZ) groups insignificant difference (P >  0.05) was observed. Both treatment modalities exhibited comparable effectiveness in controlling oral candidiasis symptoms and reducing Candida colonization as miconazole-loaded chitosan nanoparticles group showed a significant difference in the clinical improvement in respect of both signs and symptoms from baseline (70%) until the end of study at 28 days (5%) (P <  0.05) Moreover, miconazole-loaded chitosan nanoparticles, there was a significant reduction in the number of colonies forming units of Candida albicans from baseline until the end of the study at 28-day with P value <  0.000. CONCLUSIONS: This randomized controlled clinical trial and microbiological analysis demonstrate that both miconazole and miconazole-loaded chitosan nanoparticles are effective in the treatment of oral candidiasis in diabetic patients with no adverse reactions. TRIAL REGISTRATION: NCT06072716 with first registration first registration in 10/10/2023.

Guava seed activated carbon loaded calcium alginate aerogel for the adsorption of diclofenac sodium: Characterization, isotherm, kinetics, and optimization via Box-Behnken design.

This study aimed to develop a novel adsorbent designed for the removal of diclofenac sodium (DS) from water. The synthesized adsorbent, a composite sponge known as guava seeds activated carbon loaded calcium alginate (GSAC@CA aerogel), was created through the combination of powdered activated carbon derived from guava seeds and loaded onto a calcium alginate hydrogel. Characterization through SEM, XRD, FT-IR, BET, and XPS revealed a confirmed surface area of 738.82 m2/g. The investigation delved into assessing the influence of pH, initial DS concentration, and adsorbent dose on the adsorption of DS. Isotherm studies on adsorption suggested that a Langmuir model provided a good fit, indicating a monolayer adsorption process. Kinetic studies revealed a well-fitted pseudo-second-order model, shedding light on the dynamics of the reaction. The chemisorption nature was elucidated by the Dubinin-Radushkevich model, demonstrating an adsorption energy of 22.6 kJ/mol. These results affirm the potential of the GSAC@CA aerogel composite sponge as an efficient adsorbent for removing diclofenac sodium from water. Examination of the impact of temperature on the adsorption process revealed an endothermic behavior, indicating an increase in temperature. The positive change in entropy suggested the spontaneous nature of the reaction. Remarkably, the GSAC@CA aerogel composite sponge exhibited strong adsorption capabilities, achieving a maximum adsorption capacity of 489.97 mg/g. Across five consecutive cycles, the composite consistently demonstrated high-level adsorption, maintaining a removal efficiency of 87.77 %. The adsorption mechanism of diclofenac sodium (DS) on the GSAC@CA aerogel composite sponge was determined to encompass various processes, such as hydrogen bonding, π-π interactions, ion exchange, and electrostatic pore filling. Additionally, the adsorbent demonstrated successful regeneration over three cycles when applied to a real-world sample. The incorporation of the Box-Behnken design (BBD) introduced a strategic aspect to enhance adsorption outcomes, offering valuable insights for optimizing the adsorption process in practical applications.