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1.
Macromol Rapid Commun ; : e2400496, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39101719

ABSTRACT

The present study elucidates the role of annealing with electric field on lamellar crystalline structure and molecular orientation of polymer chains in ferroelectric copolymer (P(VDF-TrFE)) and ferroelectric terpolymer (P(VDF-TrFE-CFE)) spin-coated thin films. The ferroelectric polymer thin films annealed under an electric field support the growth of nanostructure with an "edge-on" lamellar crystalline structure having in-plane molecular chain orientation. The poled P(VDF-TrFE) thin films have higher remnant polarization (Pr) ≈6.2 µC cm-2 and saturation polarization (Ps) ≈8.2 µC cm-2 at an applied electric field of 250 MV/m compared to unpoled thin films having Pr ≈4.7 and Ps ≈6.2 µC cm-2. Also, poled P(VDF-TrFE) thin films show lower coercive field (Ec) ≈94 MV/m compared to an unpoled thin film having Ec ≈105 MV/m. Similarly, poled PVDF-TrFE-CFE thin film shows better ferroelectric properties having Pr ≈0.4 and Ps ≈5.7 µC cm-2 at an applied electric field of 200 MV m-1 compared to unpoled thin films having Pr ≈0.4 and Ps ≈4.1 µC cm-2. The storage energy efficiency of unpoled and poled P(VDF-TrFE-CFE) thin films is measured to be ≈75% and 80%. Annealing of ferroelectric P(VDF-TrFE) polymer thin films under an electric field demonstrates improved ferroelectric and electroactive properties.

2.
Cureus ; 16(7): e63725, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39100058

ABSTRACT

Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma (NHL). Primary CNS lymphoma (PCNSL) is a rare disease, and the subtype of Burkitt lymphoma presenting as a sole CNS lesion is an even rarer diagnosis. Acute sudden blindness is a rare presenting symptom of PCNSL or NHL in general. We present an interesting case of a four-year-old boy with dysmorphic features whose visual examination showed a sudden bilateral loss of vision. There was bilateral eye proptosis and complete ptosis. Extraocular muscles were fixed straight. The pupils were fixed and mid dilated bilaterally and there was grade 3/4 papilledema in both eyes. Neuroimaging showed a mass in the base of the skull, extending to orbits and sinuses. A cervical biopsy of the enlarged lymph nodes was taken and a histopathological diagnosis of Burkitt lymphoma was made. Genetic analysis showed a GNB1 mutation, and the patient was diagnosed with Kabuki syndrome by a pediatrician, based on characteristic dysmorphic features. Treatment with steroids and chemotherapy was initiated.

3.
Access Microbiol ; 6(8)2024.
Article in English | MEDLINE | ID: mdl-39165251

ABSTRACT

Objectives. This study aimed to determine patterns of respiratory, blood-borne and uropathogenic microbial pathogens among SARS-CoV-2-infected patients in a COVID-19-(coronavirus disease 2019) dedicated tertiary care hospital in Dhaka, Bangladesh. Design.This was a cross-sectional study. Setting. In a COVID-19-dedicated tertiary care hospital in Dhaka, Bangladesh, conducted from March to June 2021. Participants. Hospitalized individuals with COVID-19 infection regardless of age or sex. Primary and secondary outcome measures. The percentage of co-infected COVID-19 patients and the characterization of the micro-organisms responsible for co-infection served as the primary outcome measures. Finding any associations between co-infection and age, co-infection and sex and co-infection and comorbidity was the secondary outcome variable. Interventions. Not applicable. Results.Out of 79 patients, 61 % were male, and the mean age was 49.53 years. Co-infection was seen in 7.7 % of patients, out of which 5.1 % of isolates were from urine samples, followed by 2.6 % from blood. Bacteria isolated from urine were Enterococcus (2.6 %), coagulase-negative Staphylococcus (CONS) (1.3 %) and Enterobacter spp. (1.3 %). Pseudomonas spp. was the only organism isolated from blood sample. Mixed growth was found in nasopharyngeal and throat swabs, with the predominant species being Staphylococcus aureus and Streptococcus spp. At the time of data collection, 55.7 % of patients had been given antimicrobials, and 30.4 % of patients had been given a single antimicrobial. HBsAg was positive in 1.3 % of patients and none were anti-hepatitis C or dengue NS1Ag positive. Conclusion. Microbial infection has been seen to be associated with SARS-CoV-2 infections and is of great value in prescribing antimicrobials and reducing fatal outcomes of hospitalized patients.

4.
J Pharm Sci ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151795

ABSTRACT

Liver cancer is one of the aggressive primary tumors as evident by high rate of incidence and mortality. Conventional treatments (e.g. chemotherapy) suffer from various drawbacks including wide drug distribution, low localized drug concentration, and severe off-site toxicity. Therefore, they cannot satisfy the mounting need for safe and efficient cancer therapeutics, and alternative novel strategies are needed. Nano-based drug delivery systems (NDDSs) are among these novel approaches that can improve the overall therapeutic outcomes. NDDSs are designed to encapsulate drug molecules and target them specifically to liver cancer. Thus, NDDSs can selectively deliver therapeutic agents to the tumor cells and avoid distribution to off-target sites which should improve the safety profile of the active agents. Nonetheless, NDDSs should be well designed, in terms of the preparing materials, nanocarriers structure, and the targeting strategy, in order to accomplish these objectives. This review discusses the latest advances of NDDSs for cancer therapy with emphasis on the aforementioned essential design components. The review also entails the challenges associated with the clinical translation of NDDSs, and the future perspectives towards next-generation NDDSs.

6.
Cureus ; 16(7): e64684, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39149637

ABSTRACT

BACKGROUND:  Reducing the frequency of emergency department (ED) patient visits for treatment, particularly in urgent instances, is a global healthcare objective. Additionally, a more extended stay in the ED can harm a patient's prognosis during later hospitalization. This study aims to investigate the factors affecting the length of stay in the ED in a teaching hospital. METHODS: A retrospective chart review study was done between January 1, 2021, and February 31, 2021, involving 122 adult patients who had delayed ED visits to King Khalid Hospital in Najran, Saudi Arabia. Data on the patient's characteristics, visit time, and the causes for the delay based on the Canadian Triage and Acuity Scale (CTAS) were gathered and analyzed. Factors associated with more than six hours of delay were investigated in a univariate analysis. RESULT: The mean age was 52.3 ±13.5 years, and 42 (34.4%) were more than 65 years of age. More than half of the study population were female (n=66; 54.1%). Most delays occurred among CTAS 4 and 5 cases (47.5%), and 22 (18.0%) occurred during holidays. The mean delay time was 6.1 ±1.8 hours. The leading delay causes were multiple consultations with further investigations (37.7%) and conflict between the teams (36.1%). In univariate analysis, ED visiting at holiday time (OR: 0.14; 95% CI: 0.04-0.40, p <0.001) and CTAS 4 and 5 (OR: 2.22; 95% CI: 0.95-5.30, p = 0.003) significantly had more delay. Factors associated with delay in univariate analysis were multiple consultations with further investigations (OR: 2.82; 95% CI: 1.32-6.26, p = 0.013), various assessments in different ED areas with a late arrival of the specialist (OR: 0.43; 95% CI: 0.20-0.91, p = 0.042), and conflict between the teams (OR: 2.50; 95% CI: 1.17-5.54, p = 0.031). CONCLUSION: In this study, multiple assessments in different ED areas and conflict between the teams were the main factors that caused delays in ED. Implementing a timeframe monitoring system for consultations while emphasizing accelerated decision-making and disposition for patients and understanding teamwork collaboration may reduce patients' length of stay in the ED. Implementing these strategies and evaluating their impact on the length of stay in the ED requires further investigation.

7.
Pharmaceutics ; 16(7)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39065541

ABSTRACT

Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and -6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and -23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day).

8.
Sci Rep ; 14(1): 17481, 2024 07 30.
Article in English | MEDLINE | ID: mdl-39080323

ABSTRACT

Carbimazole has disadvantages on different body organs, especially the thyroid gland and, rarely, the adrenal glands. Most studies have not suggested any solution or medication for ameliorating the noxious effects of drugs on the glands. Our study focused on the production of xylooligosaccharide (XOS), which, when coadministered with carbimazole, relieves the toxic effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity. This XOS produced by Aspergillus terreus xylanase was covalently immobilized using microbial Scleroglucan gel beads, which improved the immobilization yield, efficiency, and operational stability. Over a wide pH range (6-7.5), the covalent immobilization of xylanase on scleroglucan increased xylanase activity compared to that of its free form. Additionally, the reaction temperature was increased to 65 °C. However, the immobilized enzyme demonstrated superior thermal stability, sustaining 80.22% of its original activity at 60 °C for 120 min. Additionally, the full activity of the immobilized enzyme was sustained after 12 consecutive cycles, and the activity reached 78.33% after 18 cycles. After 41 days of storage at 4 °C, the immobilized enzyme was still active at approximately 98%. The immobilized enzyme has the capability to produce xylo-oligosaccharides (XOSs). Subsequently, these XOSs can be coadministered alongside carbimazole to mitigate the adverse effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity.


Subject(s)
Adrenal Glands , Aspergillus , Carbimazole , Enzymes, Immobilized , Oligosaccharides , Aspergillus/drug effects , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Enzymes, Immobilized/metabolism , Enzymes, Immobilized/chemistry , Adrenal Glands/drug effects , Adrenal Glands/metabolism , Animals , Glucuronates/pharmacology , Oxidative Stress/drug effects , Endo-1,4-beta Xylanases/metabolism , Male , Rats , Obesity/drug therapy
9.
Cureus ; 16(6): e63252, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39070488

ABSTRACT

Background The COVID-19 pandemic significantly impacted healthcare systems globally, with cancer patients representing a particularly vulnerable group. This study aims to evaluate the influence of COVID-19 on cancer, focusing on infection rates, types of care, therapy adjustments, and factors associated with COVID-19 infection. Materials and methods This single-center retrospective analysis included adult cancer patients who underwent anticancer therapy at King Khalid Hospital in Najran, Saudi Arabia, from December 20, 2020, to January 23, 2022. Data on patient and cancer characteristics, COVID-19 specifics, treatment delays, outcomes, and factors associated with COVID-19 were collected and analyzed. Results A total of 257 chemotherapy recipients were interviewed. The mean age was 52.6 ± 14.4 years, with 44 (17.1%) over 65 years old. Females comprised 160 (62.3%) of the patients. The most common malignancies were gastrointestinal (71, 27.6%), breast (70, 27.2%), and hematological (50, 19.5%). Metastasis was present in 116 patients (45.1%). Common comorbidities included diabetes (68, 26.5%) and hypertension (55, 21.4%). Most patients (226, 87.9%) were vaccinated against COVID-19. COVID-19 tested positive in 22 patients (8.6%), with a lower infection rate in vaccinated patients (7 vs. 15, p < 0.001). Most cases were mild (18, 81.8%), with fever (19, 7.4%) and cough and fatigue (17, 6.6%) being the most common symptoms. The median time to resume treatment post-infection was 30 days. Factors associated with higher infection rates included diabetes (OR: 4.73, 95% CI: 1.94-12.03, p = 0.001), coronary artery disease (OR: 4.13, 95% CI: 1.07-13.30, p = 0.049), chronic lung disease (OR: 15.58, 95% CI: 5.37-45.79, p < 0.001), chronic liver disease (OR: 7.64, 95% CI: 2.38-22.98, p < 0.001), and multiple comorbidities (OR: 2.04, 95% CI: 1.46-2.90, p < 0.001), cancer patients who received chemotherapy (OR: 1.02, 95% CI: 0.12-12.79, p = 0.027), and immunotherapy (OR: 3.37, 95% CI:1.27-8.43, p = 0.012). Conclusion The incidence of COVID-19 in cancer patients is proportional to the prevalence in the general population of similar geographic areas. Diabetes, coronary artery disease, chronic lung disease, chronic liver disease, receiving chemotherapy or immunotherapy, and multiple comorbidities were associated with higher COVID-19 infection rates.

10.
Cureus ; 16(5): e59885, 2024 May.
Article in English | MEDLINE | ID: mdl-38854363

ABSTRACT

We present a rare and complex case of a 76-year-old male patient with a history of low-grade neuroendocrine tumor (NET) of the small intestine, status post resection, who presented with recurrence of the tumor in the liver and subsequent carcinoid heart syndrome (CHS). The recurrent liver tumor caused severe tricuspid regurgitation and CHS, highlighting the rare association between NETs and CHS, particularly in the elderly population. This case underscores the importance of multidisciplinary care and close monitoring for patients with recurrent NETs and potential cardiac complications.

11.
PLoS One ; 19(6): e0304817, 2024.
Article in English | MEDLINE | ID: mdl-38889131

ABSTRACT

Rice (Oryza sativa) stands as a crucial staple food worldwide, especially in Bangladesh, where it ranks as the third-largest producer. However, intensified cultivation has made high-yielding rice varieties susceptible to various biotic stresses, notably sheath blight caused by Rhizoctonia solani, which inflicts significant yield losses annually. Traditional fungicides, though effective, pose environmental and health risks. To address this, nanotechnology emerges as a promising avenue, leveraging the antimicrobial properties of nanoparticles like silver nanoparticles (AgNPs). This study explored the green synthesis of AgNPs using Ipomoea carnea leaf extract and silver nitrate (AgNO3), and also examined their efficacy against sheath blight disease in rice. The biosynthesized AgNPs were characterized through various analytical techniques such as UV-vis spectrophotometer, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Particle size analyzer, Zeta potential, Scanning Electron Microscope (SEM), Field Emission Scanning Electron Microscope (FESEM), Transmission Electron Microscope (TEM) for confirming their successful production and crystalline nature of nanoparticles. The results of UV-visible spectrophotometers revealed an absorption peak ranging from 421 to 434 nm, validated the synthesis of AgNPs in the solution. XRD, DLS, and TEM estimated AgNPs sizes were ~45 nm, 66.2nm, and 46.38 to 73.81 nm, respectively. SEM and FESEM demonstrated that the synthesized AgNPs were spherical in shape. In vitro assays demonstrated the significant inhibitory effects of AgNPs on mycelial growth of Rhizoctonia solani, particularly at higher concentrations and pH levels. Further greenhouse and field experiments validated the antifungal efficacy of AgNPs against sheath blight disease in rice, exhibiting comparable effectiveness to commercial fungicides. The findings highlight the potential of AgNPs as a sustainable and effective alternative for managing rice sheath blight disease, offering a safer solution amidst environmental concerns associated with conventional fungicides.


Subject(s)
Green Chemistry Technology , Metal Nanoparticles , Oryza , Plant Diseases , Rhizoctonia , Silver , Rhizoctonia/drug effects , Oryza/microbiology , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Plant Diseases/microbiology , Plant Diseases/prevention & control , X-Ray Diffraction , Plant Extracts/chemistry , Plant Extracts/pharmacology , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry
12.
Mymensingh Med J ; 33(3): 741-749, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38944716

ABSTRACT

Coronavirus disease 2019 (Covid-19) disease have been associated with significant mortality amongst doctors globally including Bangladesh. To delineate the clinico-epidemiological characteristics of the physician affected with Covid-19 was the objective of the study. This cross-sectional 'Facebook' based survey was conducted in the period of August 2020 to September 2020. Snowball sampling methods was followed. A total of 151 physicians affected with Covid-19 participated in this survey. Self-reported perceived severity scale (zero meaning not severe at all and ten denoting the most severe) was used. Collected data were analyzed by SPSS 25.0. Among the participants, the majority were male, 98(64.9%). The most prevalent affected age groups were 24-35 years 131(86.8%). Approximately 45.0% worked in COVID dedicated hospital. Entry-level physicians (Medical Officer or Assistant Surgeon) were the most affected 117(94.4%). One-third of the physicians had at least the one co-morbidity. Bronchial asthma, obesity and diabetes were the most frequent. Predominate symptoms of the infection were fever 94(62.3%), cough 94(62.3%) and myalgia 92(60.9%). Half of the participants had sore throat, anosmia, gastro-intestinal symptoms and one-third of the patients developed dyspnea. Perceived severity of the symptoms ranged between 2 and 6. The pattern of drug use to prevent the Covid-19 showed no uniformity. However, intake of Zinc, Vitamin C, Vitamin D, antihistamine and Ivermectin was found in 74.8%, 67.5%, 41.7%, 49.0% and 37.7% respectively. As the current pandemic continues to evolve, physicians must be equipped with appropriate knowledge, skills and must be cautious on the prevention measures against Covid-19.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Male , Female , Cross-Sectional Studies , Adult , Bangladesh/epidemiology , Physicians/statistics & numerical data , Middle Aged , SARS-CoV-2 , Young Adult , Comorbidity , Severity of Illness Index , Surveys and Questionnaires
13.
Int J Biol Macromol ; 272(Pt 2): 132864, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38844272

ABSTRACT

Scleroglucan is a notable member of the ß-glucan microbial polysaccharides with a long tradition of industrial and therapeutic use. The local strain, previously identified as Athelia rolfsii TEMG MH 236106 produced an appreciable amount of scleroglucan using glucose as a carbon source and yeast extract as a nitrogen source. Plackett-Burman design was employed to effectively screen critical medium composition, culture, and fermentation conditions. Athelia rolfsii TEMG MH 236106 produced the maximum amount of scleroglucan (18.12 g/L) with a 45.3 % glucose conversion. Out of the eleven variables, the most effective factors showing a high level of significance are as follows: glucose, yeast extract, citric acid, inoculum disc numbers, culture volume and incubation time. An update to maximize scleroglucan production in the central composite design for four parameters (glucose and yeast extract concentrations, disc number, medium volume and incubation time) with 31 runs was applied and the production of scleroglucan reached its maximum at 31.56 g/L with 78.9 % glucose conversion. Three models of Sclg-5-fluorouracil complexes have been employed to study in vitro drug release investigations. Hence, the Sclg-5-FU (5 and 10 mg/mL) models appeared to be the most suitable for drug administration due to their concentration and distribution within capsules.


Subject(s)
Fluorouracil , Glucans , Glucans/chemistry , Fluorouracil/pharmacology , Fluorouracil/metabolism , Fermentation , Drug Liberation , Glucose/metabolism , Culture Media/chemistry
14.
Cureus ; 16(5): e59608, 2024 May.
Article in English | MEDLINE | ID: mdl-38832203

ABSTRACT

BACKGROUND: Chemotherapy-related cardiotoxicity can exhibit several patterns of functional, structural, and vascular complications. This study aims to identify the patterns and the factors associated with cardiotoxicity in cancer patients. METHOD: A retrospective cross-sectional analysis of 96 adult cancer patients undergoing anticancer therapy was investigated at King Khalid Hospital in Najran, Saudi Arabia, from May 2022 to April 2023. The data on patient and cancer characteristics, treatment, and outcomes were collected and analyzed. Factors associated with cardiotoxicity were investigated through univariate analyses using odds ratio (OR) and 95% confidence interval (CI). RESULTS:  Among the 96 cancer patients in the study, cardiotoxicity occurred in 12 individuals (12.5%). The mean age was 57.0 ± 13.3 years (range: 32-81 years), with 32 (33.3%) being above 65 years. The most common comorbidities were diabetes (n=48; 50%), followed by hypertension (n=32; 33.3%), and dyslipidemia (n=20; 20.8%). The most common cancers were gastrointestinal cancer (n=32; 33.3%), followed by breast cancer (n=22; 22.9%) and lymphoma (n=14; 14.6%). Females were disproportionately affected (64.6%), with 57.3% of them in the metastatic stage. The majority of patients (90.6%) had normal ejection fraction before chemotherapy initiation. In univariate analysis, current smoking (OR: 7.00; 95%CI: 1.94-25.25, p= 0.003), history of percutaneous cardiac intervention (OR: 40.24; 95%CI: 1.80-896.26, p= 0.019), diabetes (OR: 6.05; 95%CI: 1.24-29.32, p= 0.025), renal failure (OR: 8.20; 95%CI: 0.91-74.88, p= 0.046), dyslipidemia (OR: 5.00; 95 CI: 1.38-18.32, p=0.012), anthracycline use (OR: 18.33; 95%CI: 4.36-126.55, p <0.001), trastuzumab use (OR: 25.00; 95%CI: 6.25-129.86, p < 0.001), and increased chemotherapy cycles number (> 10 cycles) (OR: 73.00; 95%CI: 8.56- 622.36, p < 0.001) were associated with cardiotoxicity. Additionally, beta-blocker use was associated with lower rates of cardiotoxicity (OR: 0.17; 95%CI: 0.036-0.84, p= 0.029). CONCLUSIONS: The incidence of cardiotoxicity among cancer patients treated with chemotherapy is modest, difficult to predict, and independent of baseline cardiac systolic functions. Factors associated with cardiotoxicity include smoking, history of percutaneous cardiac intervention, diabetes, renal failure, dyslipidemia, anthracycline or trastuzumab use, and increased chemotherapy cycle numbers. A combination of various anticancer drugs and chemotherapy may dramatically raise the risk of cardiotoxicity in cancer patients. As a result, patients receiving high-risk cardiotoxic drugs should be monitored with caution to avoid drug-related cardiotoxicity. Furthermore, proactive treatment techniques aiming at reducing the possible cardiotoxic effects of anticancer therapy are critical.

15.
J Biol Chem ; 300(7): 107423, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38815864

ABSTRACT

Recent research has identified the mechanistic Target of Rapamycin Complex 2 (mTORC2) as a conserved direct effector of Ras proteins. While previous studies suggested the involvement of the Switch I (SWI) effector domain of Ras in binding mTORC2 components, the regulation of the Ras-mTORC2 pathway is not entirely understood. In Dictyostelium, mTORC2 is selectively activated by the Ras protein RasC, and the RasC-mTORC2 pathway then mediates chemotaxis to cAMP and cellular aggregation by regulating the actin cytoskeleton and promoting cAMP signal relay. Here, we investigated the role of specific residues in RasC's SWI, C-terminal allosteric domain, and hypervariable region (HVR) related to mTORC2 activation. Interestingly, our results suggest that RasC SWI residue A31, which was previously implicated in RasC-mediated aggregation, regulates RasC's specific activation by the Aimless RasGEF. On the other hand, our investigation identified a crucial role for RasC SWI residue T36, with secondary contributions from E38 and allosteric domain residues. Finally, we found that conserved basic residues and the adjacent prenylation site in the HVR, which are crucial for RasC's membrane localization, are essential for RasC-mTORC2 pathway activation by allowing for both RasC's own cAMP-induced activation and its subsequent activation of mTORC2. Therefore, our findings revealed new determinants of RasC-mTORC2 pathway specificity in Dictyostelium, contributing to a deeper understanding of Ras signaling regulation in eukaryotic cells.


Subject(s)
Dictyostelium , Mechanistic Target of Rapamycin Complex 2 , Signal Transduction , ras Proteins , Dictyostelium/metabolism , Dictyostelium/genetics , Mechanistic Target of Rapamycin Complex 2/metabolism , Mechanistic Target of Rapamycin Complex 2/genetics , ras Proteins/metabolism , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Protozoan Proteins/chemistry , Cyclic AMP/metabolism
16.
World J Microbiol Biotechnol ; 40(7): 202, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743315

ABSTRACT

Currently, heavy metal-resistant (HMR) marine actinomycetes have attracted much attention worldwide due to their unique capabilities. In this study, 27 marine-derived actinomycetes were isolated from coastal beaches in the Arabian Gulf of Al-Jubail in Saudi Arabia and screened for resistance to 100 mg/L of the heavy metals Cd2+, Cr6+, Cu2+, Fe2+, Pb2+, and Ni2+ using different assay techniques. Six isolates were selected as HMRs, of which two isolates, JJB5 and JJB11, exhibited the highest maximum tolerance concentrations (200- > 300 mg/L). Both isolates were the highest among six-HMR screened for their biodegradation potential of plastics low-density polyethylene, polystyrene, and polyvinyl chloride, recording the highest weight loss (15 ± 1.22 - 65 ± 1.2%) in their thin films. They also showed the highest biodegradability of the pesticides acetamiprid, chlordane, hexachlorocyclohexane, indoxacarb and lindane, indicating promising removal capacities (95.70-100%) for acetamiprid and indoxacarb using HPLC analysis. Additionally, the cell-free filtrate (CFF) of both isolates displayed the highest antimicrobial activity among the six-HMR screened against a variety of microbial test strains, recording the highest inhibition zone diameters (13.76 ± 0.66 - 26.0 ± 1.13 mm). GC‒MS analyses of the ethyl acetate extract of their CFFs revealed the presence of diverse chemical compounds with a multitude of remarkable biological activities. Based on their spore morphology and wall-chemotype, they were assigned to the nocardioform-actinomycetes. Furthermore, their phenotypic characteristics, together with 16S rRNA gene sequencing (OR121525-OR121526), revealed them as Nocardia harenae JJB5 and Amycolatopsis marina JJB11. Our results suggest that marine HMR actinomycetes are promising candidates for various biotechnological applications.


Subject(s)
Biodegradation, Environmental , Metals, Heavy , Microbial Sensitivity Tests , Nocardia , RNA, Ribosomal, 16S , Metals, Heavy/metabolism , RNA, Ribosomal, 16S/genetics , Nocardia/isolation & purification , Nocardia/genetics , Nocardia/metabolism , Saudi Arabia , Anti-Bacterial Agents/pharmacology , Phylogeny , Actinobacteria/metabolism , Actinobacteria/isolation & purification , Actinobacteria/genetics , Actinobacteria/classification , Water Pollutants, Chemical/metabolism , Seawater/microbiology , Pesticides/metabolism , Drug Resistance, Bacterial
17.
Cureus ; 16(4): e58602, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38770472

ABSTRACT

BACKGROUND: Lung cancer is one of the top causes of cancer deaths globally, including in Saudi Arabia. Although several prognostic markers have been established, the clinical features and outcomes of lung cancer in Saudi Arabia are not well understood. This study aimed to describe the clinical and therapeutic characteristics of advanced lung cancer in Najran, Saudi Arabia. METHOD: A retrospective chart review of 44 patients diagnosed with advanced lung cancer between June 2018 and September 2021 and treated at the Oncology Center of King Khalid Hospital in Najran City, Saudi Arabia. The clinicopathological features, treatment used, response, and survival outcomes were collected and analyzed. RESULT: The mean age was 69.3 ± 10.7 years, most of them (n = 35, 79.5%) were male and older than 70 years (n = 24, 54.5%). Adenocarcinoma was the most observed cancer (n = 35, 79.5%), followed by squamous cell carcinoma in six (13.6%). Most cases (n = 42, 95.5%) were in stage IV. Epidermal growth factor receptor (EGFR) mutations were positive in two (4.5%) cases and ALK mutation was positive in two (4.5%) cases. Metastasis to pleura with pleural effusion was the common presentation (n = 41, 93%). Chemotherapy was administered as the first line in 19 cases (43.2%) while 25 cases (56.8%) received chemoimmunotherapy. The commonest chemoimmunotherapy regimen used was carboplatin-pemetrexed-pembrolizumab in 16 (36.4%), followed by carboplatin-paclitaxel-pembrolizumab in 9 (20.5%) cases. The response to initial systemic therapy was as follows disease progression, stable disease, and complete remission in 10 (22.7%), 33 (75.0%), and 1 (2.3%), respectively. Median progression-free survival was 8.7 months (interquartile range (IQR): 5.7-11.4), and the median overall survival was 12.3 months (IQR: 11.1-13.4). Among the total documented 36 (81.8%) dead cases, disease progression was the main cause of death in 25 cases (56.8%). Using chemoimmunotherapy as the first-line therapy was associated with numerical survival improvement compared to using chemotherapy alone (HR: 0.75; 95% CI: 0.39-1.46) however, it was not statistically significant (p = 0.397). CONCLUSION: In this study, the majority of lung cancer patients were male and over 70 years old. Adenocarcinoma was the most common histological type. Metastasis to pleura with pleural effusion was the common presentation. The most common treatment used was chemoimmunotherapy with a regimen of carboplatin-pemetrexed-pembrolizumab. Addressing the possible causes of delayed diagnosis of lung cancer is crucial for improved survival outcomes.

18.
Cureus ; 16(3): e56650, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38646208

ABSTRACT

Background Bronchopulmonary dysplasia (BPD) is a significant complication in extremely preterm infants. Therefore, early diagnosis of BPD is important for planning treatment strategies. In this study, we aimed to assess the predictive efficacy of the Respiratory Severity Score (RSS) in determining severe BPD or death outcomes in very preterm infants. Methodology This retrospective study included preterm infants born with a gestational age of ≤30 weeks. The inclusion criteria comprised individuals who were mechanically ventilated (<1 week) during the first four weeks of life. Any patients who died during the first seven days of life were excluded. RSS values were recorded on days 3, 14, 21, and 28 of life. Multivariate logistic regression was used to identify a correlation between RSS and patient outcomes. Results A total of 154 infants were included in the analysis, of whom 82 (53.24%) developed severe BPD and 38 (24.67%) died. RSS was higher in patients who either died or developed severe BPD compared to those who survived. The multivariate logistic regression analysis revealed that RSSs at postnatal day 14 (odds ratio (OR) = 3.970; 95% confidence interval (CI) = 1.114-14.147; p < 0.05), day 21 (OR = 6.201; 95% CI = 1.937-19.851; p < 0.05), and day 28 (OR = 8.925; 95% CI = 3.331-28.383; p < 0.05) was significantly associated with a higher risk of death or severe BPD. Conclusions The findings of the present study revealed that RSS can help predict the risk of severe BPD in very preterm infants.

19.
J Environ Manage ; 358: 120918, 2024 May.
Article in English | MEDLINE | ID: mdl-38643625

ABSTRACT

The aging process of microplastics (MPs) could significantly change their physical and chemical characteristics and impact their migration behavior in soil. However, the complex effects of different cations and humic acids (HA) on the migration of aged MPs through saturated media are not clear. In this research, the migration and retention of pristine/aged PSMPs (polystyrene microplastics) under combined effects of cations (Na+, Ca2+) (ionic strength = 10 mM) and HA (0, 5, 15 mg/L) were investigated and analyzed in conjunction with the two-site kinetic retention model and DLVO theory. The findings showed that the aging process accelerated PSMPs migration under all tested conditions. Aged PSMPs were less susceptible to Ca2+ than pristine PSMPs. Under Ca2+ conditions, pristine/aged PSMPs showed higher retention than under Na+ conditions in the absence of HA. Furthermore, under Na+ conditions, the migration of aged PSMPs significantly increased at higher concentrations of HA. However, under Ca2+ conditions, the migration of aged PSMPs decreased significantly at higher concentrations of HA. In higher HA conditions, HA, Ca2+, and PSMPs interact to cause larger aggregations, resulting in the sedimentation of aged PSMPs. The DLVO calculations and two-site kinetic retention models' results showed the detention of PSMPs was irreversible under higher HA conditions (15 mg/L) with Ca2+, and aged PSMPs were more susceptible to clogging. These findings may help to understand the potential risk of migration behavior of PSMPs in the soil-groundwater environment.


Subject(s)
Cations , Humic Substances , Microplastics , Polystyrenes , Polystyrenes/chemistry , Microplastics/toxicity , Cations/chemistry , Porosity , Kinetics , Soil/chemistry
20.
Int J Pharm X ; 7: 100245, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38633410

ABSTRACT

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

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