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1.
Biochim Biophys Acta Gen Subj ; 1868(9): 130667, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38971261

ABSTRACT

The Araceae family boasts >3000 species of flowering plants that thrive across the tropics. Among the focal points of study within this family are lectins, proteins with affinity for binding carbohydrates. This review endeavors to gather data gleaned from numerous studies conducted over the past three decades on lectins extracted from Araceae plants. Our examination spans their extraction and purification methods, their specific interactions with carbohydrates, their molecular structures, and various physicochemical characteristics. Furthermore, we investigated the biological activities of these lectins and investigated the outcomes of cloning their genes. Despite their apparent similarities, these lectins exhibit notable distinctions, particularly regarding their unique preferences in interacting with erythrocytes from animals and humans, their sugar affinities, the critical amino acids for their functionality, the molecular weights of their subunits and their respective topologies, and ultimately, their dimerization and 3D ß-prism-II structure, which reportedly diverge from those observed in other GNA-related lectins. These discrepancies not only deepen our understanding of monocot lectins but also render these proteins inherently captivating. This review marks the inaugural attempt at consolidating almost all published reports on lectins from the Araceae family, with the aim of furnishing glycobiology scientists with essential insights into potential laboratory challenges, the characteristics of these lectins, and avenues for future research.


Subject(s)
Plant Lectins , Plant Lectins/chemistry , Plant Lectins/metabolism , Humans , Animals
2.
Cureus ; 16(5): e60217, 2024 May.
Article in English | MEDLINE | ID: mdl-38868285

ABSTRACT

Salmonella typhi (S. typhi) infections typically present with fever and gastrointestinal symptoms. This case report on S. typhi enteritis documents atypical clinical, radiological, and endoscopic findings raising diagnostic challenges. A 31-year-old male in the Kingdom of Saudi Arabia (KSA) presented with severe abdominal pain, vomiting, bloody diarrhea, and no fever. Initial diagnosis included amebiasis and other gastroenteritis infections. Despite treatment with ciprofloxacin and metronidazole, the patient's condition did not improve, and he kept having intractable abdominal pain and vomiting. Subsequent investigations, including abdominal ultrasound and esophagogastroduodenoscopy, revealed extensive and rapidly progressive intestinal inflammation with wall thickening and ascites. Stool culture eventually identified a multidrug-resistant strain of S. typhi, sensitive only to ceftriaxone. Treatment with ceftriaxone and continuous infusion of proton pump inhibitor (PPI) led to significant improvement. The absence of fever in the context of bloody diarrhea, and the rapid development of ascites not improving with first-line treatment of gastroenteritis, led to the search for other diagnoses such as inflammatory bowel syndromes or tuberculosis. The presentation of diffuse intestinal wall thickening with intractable vomiting, bloody diarrhea, and progressively increasing ascites is not frequently encountered with S. typhi. The case also underscores the growing concern of antibiotic-resistant S. typhi strains. The patient's response to targeted antibiotic therapy emphasizes the importance of accurate microbial identification and susceptibility testing in managing infectious diseases. This case report illustrates an atypical presentation of S. typhi enteritis with progressively increasing ascites and increased intestinal wall thickening. The uncommon complicated clinical picture led to challenges in diagnosis and management. It emphasizes the need for high clinical suspicion and comprehensive diagnostic approaches in atypical cases of common infections, especially in the context of increasing antibiotic resistance.

3.
Article in English | MEDLINE | ID: mdl-38904564

ABSTRACT

INTRODUCTION: The accuracy of tooth segmentation in intraoral scans is crucial for performing virtual setups and appliance fabrication. Hence, the objective of this study was to estimate and compare the accuracy of automated tooth segmentation generated by the artificial intelligence of dentOne software (DIORCO Co, Ltd, Yongin, South Korea) and Medit Ortho Simulation software (Medit Corp, Seoul, South Korea). METHODS: Twelve maxillary and mandibular pretreatment dental scan sets comprising 286 teeth were collected for this investigation from the archives of the Department of Orthodontics, Faculty of Dentistry, Alexandria University. The scans were imported as standard tessellation language files into both dentOne and Medit Ortho Simulation software. Automatic segmentation was run on each software. The number of successfully segmented teeth vs failed segmentations was recorded to determine the success rate of automated segmentation of each program. Evaluation of success and/or failure was based on the software's identification of the teeth and the quality of the segmentation. The mesiodistal tooth width measurements after segmentation using both tested software programs were compared with those measured on the unsegmented scan using Meshmixer software (Autodesk, San Rafael, Calif). The unsegmented scans served as the reference standard. RESULTS: A total of 288 teeth were examined. Successful identification rates were 99% and 98.3% for Medit and dentOne, respectively. Success rates of segmenting the lingual surfaces of incisors were significantly higher in Medit than in dentOne (93.7% vs 66.7%, respectively; P <0.001). DentOne overestimated the mesiodistal width of canines (0.11 mm, P = 0.032), premolars (0.22 mm, P < 0.001), and molars (0.14 mm, P = 0.043) compared with the reference standard, whereas Medit overestimated the mesiodistal width of premolars only (0.13 mm, P = 0.006). Bland-Altman plots showed that mesiodistal tooth width agreement limits exceeded 0.2 mm between each software and the reference standard. CONCLUSIONS: Both artificial intelligence-segmentation software demonstrated acceptable accuracy in tooth segmentation. There is a need for improvement in segmenting incisor lingual tooth surfaces in dentOne. Both software programs tended to overestimate the mesiodistal widths of segmented teeth, particularly the premolars. Artificial intelligence-segmentation needs to be manually adjusted by the operator to ensure accuracy. However, this still does not solve the problem of proximal surface reconstruction by the software.

4.
BMC Oral Health ; 24(1): 609, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796434

ABSTRACT

BACKGROUND: High speed electric handpieces have recently been growing in popularity among dental professionals. Advantages include smoother surface preparation and increased cutting efficiency. AIM: The primary objective was to compare enamel surface roughness following resin cleanup after bracket debonding using highspeed air turbine versus electric handpiece. The secondary objective was to record the time needed for resin-clean up. METHOD: Forty deidentified freshly extracted human premolars were cleaned and sectioned at the cement-enamel junction. The crowns were embedded in acrylic blocks. Enamel surface roughness parameters (Ra, Rz, Rp and Rv) were measured using a stylus profilometer. Brackets were bonded using a light-cure orthodontic adhesive and stored in distilled water for 24 h. Following bracket debonding, the specimens were randomly divided into 2 groups: First group: resin clean-up was carried out using a 12-fluted carbide bur mounted on a high-speed air turbine; and second group: where an electric handpiece was used. Surface roughness parameters were measured following resin clean up and after polishing using pumice and a rubber cup. Time needed for resin clean-up was recorded. Differences in enamel surface roughness and time between groups were compared using repeated measures ANOVA and independent samples t-test, respectively at P ≤ 0.05. RESULTS: The electric handpiece groups showed significantly higher values for Ra, Rz and Rp both following resin cleanup and polishing. Time taken for resin cleanup was significantly longer for the electric handpiece group. CONCLUSION: Considering both surface roughness and time, electric handpiece do not seem to add greater effectiveness or efficiency to resin cleanup following orthodontic bracket debonding.


Subject(s)
Dental Debonding , Dental Enamel , Dental High-Speed Equipment , Surface Properties , Humans , Dental Debonding/methods , In Vitro Techniques , Resin Cements/chemistry , Orthodontic Brackets , Time Factors , Bicuspid , Dental Polishing/methods
5.
Vaccine ; 42(12): 3033-3038, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38594122

ABSTRACT

INTRODUCTION: Despite being a preventable and treatable disease, cholera remains a public health problem in Sudan. The objective of the outbreak investigation was to identify associated risk factors that would help institute appropriate control measures. MATERIAL AND METHODS: A case control study design was chosen to identify the risk factors for cholera in Gadarif State. RESULTS: Multi-variate analysis of identified two risk factors and three preventive factors for cholera in Gadarif City. RISK FACTORS: Buying foods or drinks from street vendors (OR = 71.36), 95 % CI: 16.58-307.14), living in an urban setting (Gadarif City) (OR = 5.38), 95 % CI: 2.10-13.81); and the preventive factors were: Washing hands with water after defecation but without soap (OR = 0.16), 95 % CI: 0.04-0.63) or with soap (OR = 0.01), 95 % CI: 0.00-0.03), washing hands before eating (OR = 0.15), 95 % CI: 0.05-0.51) and taking Oral Cholera Vaccine (OCV) (OR = 0.19, 95 % CI: 0.08-0.44). The effectiveness of OCV (VE) was (Unadjusted VE: 80 %, 95 % CI: 69 %-87 %) or (Adjusted VE = 81.0 %, 95 % CI: 56.0 %-92.0 %). DISCUSSION: Cholera outbreaks, especially in the setting of a complex humanitarian crises, can spread rapidly, resulting in many deaths, and quickly become a public health crisis. Implementation of a community-wide vaccination campaign using OCV as early as possible during the outbreak while implementing other control measures to target hotspots and at-risk populations would expedite halting outbreaks of cholera and save lives.


Subject(s)
Cholera Vaccines , Cholera , Humans , Cholera/epidemiology , Cholera/prevention & control , Case-Control Studies , Soaps , Administration, Oral , Disease Outbreaks/prevention & control
6.
Health Sci Rep ; 7(3): e1980, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38486685

ABSTRACT

Background and Aim: Conflicts, akin to other crises, disrupt lives and healthcare infrastructure, disproportionately affecting vulnerable individuals. The ongoing Sudanese conflict, initiated on April 15, 2023, between the Sudanese Armed Forces (SAF) and the Rapid Support Force (RSF), triggers significant population displacement, healthcare facility closures, and a scarcity of medical resources. Amid the intense conflict in Khartoum, reports of deceased individuals in the streets heighten concerns about public health, emphasizing the gravity of the situation. This crisis compounds the challenges faced by Sudan's already fragile healthcare system, impacting over 5 million displaced individuals, including those reliant on life-saving hemodialysis sessions. This commentary aims to illuminate the challenges confronting kidney dialysis patients in war-torn Sudan, emphasizing the impact on the Al-Goled hemodialysis center. Methodology: This commentary relies on reports from the American Society of Nephrology (ASN), European Renal Association (ERA), and The International Society of Nephrology (ISN), along with recent journal articles discussing the consequences of ongoing conflicts. Personal observations in Al-Goled contribute to the insights, and data from the Al-Goled hemodialysis center in Sudan illuminate the struggles faced by kidney dialysis patients during the conflict, presented as a case study. Results: Kidney dialysis patients, crucial for regular hemodialysis sessions, confront severe challenges due to the overwhelming conflict. With an estimated 8000 kidney failure patients in Sudan, disruptions in healthcare services, targeted attacks on medical staff, and a shortage of resources exacerbate their plight. The Al-Goled hemodialysis center, initially designed for 30 daily sessions, experiences a surge in demand, accommodating 85 patients daily-an alarming 183% increase. Limited resources, machine malfunctions, and a shortage of medications contribute to the loss of 13 patients' lives. Conclusions: The conflict in Sudan disproportionately impacts kidney dialysis patients, causing disruptions in essential healthcare services. The surge in demand at the Al-Goled center underscores the broader impact on healthcare institutions nationwide. Local efforts to source medical supplies face bureaucratic hurdles and complex exportation procedures, impeding support for kidney patients. Patients, once receiving 3 weekly sessions, now struggle to secure even one, jeopardizing their well-being. Urgent international intervention is needed to cease the conflict and ensure the safety of healthcare facilities, especially for vulnerable populations like kidney dialysis patients.

7.
Front Pharmacol ; 15: 1322865, 2024.
Article in English | MEDLINE | ID: mdl-38464729

ABSTRACT

Background and aims: Cancer continues to be a significant source of both illness and death on a global scale, traditional medicinal plants continue to serve as a fundamental resource of natural bioactive compounds as an alternative source of remedies. Although there have been numerous studies on the therapeutic role of Phoenix dactylifera, the study of the role of peptides has not been thoroughly investigated. This study aimed to investigate the anticancer activity of lectin peptides from P. dactylifera using in silico and in vivo analysis. Methods: Different computational tools were used to extract and predict anticancer peptides from the true lectins of P. dactylifera. Nine peptides that are bioactive substances have been investigated for their anticancer activity against MCF-7 and T47D (two forms of breast cancer). To counteract the unfavorable effects of mitotane, the most potent peptides (U3 and U7) were combined with it and assessed for anticancer activity against MCF-7 and HepG2. Results: In silico analysis revealed that nine peptides were predicted with anticancer activity. In cell lines, the lowest IC50 values were measured in U3 and U7 against MCF-7 and T47D cells. U3 or U7 in combination with mitotane demonstrated the lowest IC50 against MCF-7 and HepG2. The maximum level of cell proliferation inhibition was 22% when U3 (500 µg/mL) and 25 µg/mL mitotane were combined, compared to 41% when 25 µg/mL mitotane was used alone. When mitotane and U3 or U7 were combined, it was shown that these bioactive substances worked synergistically with mitotane to lessen its negative effects. The combination of peptides and mitotane could be regarded as an efficient chemotherapeutic medication having these bioactive properties for treating a variety of tumors while enhancing the reduction of side effects.

8.
Food Chem ; 442: 138435, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38266415

ABSTRACT

A new analytical method for measuring copper in food and water was developed and validated, employing a solid-phase extraction (SPE) technique combined with digital-image-based (DIB) detection. A novel magnetic adsorbent of zinc ferrite/Citrullus colocynthis biochar (ZF@C.BC) was used to preconcentrate copper. A magnetic tip was used to separate the copper-loaded adsorbent from the extraction medium and to dispense it to the DIB plate. In-situ desorption and development of the spot color with iodide-starch reagent were carried out, and a digital image of the developed spots was captured using a smartphone and processed using ImageJ software. The copper adsorption capacity was 91.3 mg g-1. Desorption was effected using a 0.3 mol L-1 hydrochloric acid. The preconcentration factor was 300, the limit of detection was 4.8 µg L-1, the linearity was 16-600 µg L-1 and the sample throughput was 12 h-1. The developed approach was validated by analyzing food and water samples, confirming recoveries ≥ 91 % and 88 %, respectively, with RSD ≤ 8.4 %, n = 3.


Subject(s)
Copper , Water , Adsorption , Food , Solid Phase Extraction/methods , Magnetic Phenomena
10.
Nutr Rev ; 82(2): 240-243, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-37172268

ABSTRACT

Liver diseases, especially the chronic type, are a global concern. There is a growing interest in the intermittent fasting model due to its presumed health benefits. Ramadan fasting, although religious fasting, is one of the best examples of intermittent fasting, with some differences, and is observed by more than 1 billion Muslims around the world. This month follows the Arabic Hijri calendar, which is 12 days shorter than the Gregorian calendar; hence, this entire month of fasting may occur in any season of the year. There is evidence that many patients with chronic liver disease are prone to adverse events upon observing this month of continuous intermittent fasting, particularly during the hot summer with prolonged hours of fasting, if they are not adequately addressed and prevented from fasting. There is a need to sound the alarm to develop a risk-assessment tool to omit vulnerable patients with chronic liver disease-who are exempted on religious grounds from observing this pattern of fasting.


Subject(s)
Intermittent Fasting , Liver Diseases , Humans , Fasting , Islam
12.
Biochemistry (Mosc) ; 88(11): 1956-1969, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38105212

ABSTRACT

Euphorbiaceae, also known as the spurge family, is a large group of flowering plants. Despite being tropical natives, they are now widespread. Due to its medicinal and commercial importance, this family of plants attracted a lot of attention in the scientific community. The distinctive characteristic of the family is production of milky latex, which is a rich source of several lectins, the proteins that bind carbohydrates. Although their function is unclear, they are believed to defend plants against damaging phytopathogenic microorganisms, insects, and predatory animals. Additionally, they serve as crucial metabolic regulators under a variety of stressors. Detection, separation, purification, and characterization of lectins from the Euphorbiaceae family - mostly from the latex of plants - began over 40 years ago. This effort produced over 35 original research papers that were published. However, no systematic review that compiles these published data has been presented yet. This review summarizes and describes several procedures and protocols employed for extraction and purification of lectins belonging to this family. Physicochemical properties and biological activities of the lectins, along with their medicinal and pharmacological properties, have also been analyzed. Additionally, using examples of ricin and ricin agglutinin, we have structurally analyzed characteristics of the lectin known as Ribosome Inactivating Protein Type II (RIP-Type II) that belongs to this family. We anticipate that this review article will offer a useful compendium of information on this important family of lectins, show the scientists involved in lectin research the gaps in our knowledge, and offer insights for future research.


Subject(s)
Euphorbiaceae , Ricin , Animals , Ricin/chemistry , Plant Lectins/pharmacology , Latex/chemistry , Plants
13.
Environ Pollut ; 339: 122741, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37839684

ABSTRACT

The present work aims to evaluate the impact of Lake Manzala development, started in 2017, on lake water quality and biomarkers of Lake Oreochromis niloticus and Biomphalaria alexandrina samples from Dakahlia and Port Said during 2021 and compare it with the results of a series of studies concerning the same criteria in Lake Manzala during 2015. Results showed a remarkable increase in water EC, indicating a higher water exchange with the sea, a significant decrease in Pb, Cd, Cu, and Zn levels in water samples, and a remarkable decline in Cd and Pb bioaccumulation in all fish and snail samples. Macroinvertebrate samples showed higher taxa richness than in 2015, indicating biologically improved lake water quality. Results showed no trematode transmission, while there were natural infections in B. alexandrina snails during 2015. Biochemically, liver enzymes and hematological criteria in fish and snail samples during 2021 showed levels nearer to control at Port Said, indicating a less stressed liver and more healthy specimens than in 2015. Histopathological examination of fish organs (except spleen) and snail tissues pointed to their improved tissue architecture in Port Said than that of Dakahlia (2021). However, the 2021 samples were better than those of 2015. The immunohistochemical study showed higher expression of IL-6 in Dakahlia samples than the other samples, denoting higher tissue inflammation and humoral immune response. So, all the examined criteria indicated that Manzala Lake is positively impacted by the developmental and purification process, especially in Port Said.


Subject(s)
Cichlids , Water Pollutants, Chemical , Animals , Ecosystem , Lakes , Egypt , Cadmium , Lead , Water Pollutants, Chemical/analysis , Environmental Monitoring , Snails/metabolism , Biomarkers , Cichlids/metabolism
14.
Behav Res Methods ; 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37537491

ABSTRACT

Mental fatigue is a commonplace human experience which is the focus of a growing body of research. Whilst researchers in numerous disciplines have attempted to uncover the origins, nature, and effects of mental fatigue, the literature is marked by many contradictory findings. We identified two major methodological problems for mental fatigue research. First, researchers rarely use objective measures of mental fatigue. Instead, they rely heavily on subjective reports as evidence that mental fatigue has been induced in participants. We aimed to develop a task which led to not only a subjective increase in mental fatigue, but a corresponding performance decrement in the mentally fatiguing task as an objective measure. Secondly, current mental fatigue paradigms have low ecological validity - in most prior studies participants have been fatigued with a single repetitive task such as the n-back or Stroop. To move towards a more ecologically valid paradigm, our participants undertook a battery of diverse cognitive tasks designed to challenge different aspects of executive function. The AX-CPT, n-back, mental rotation, and visual search tasks were chosen to challenge response inhibition, working memory, spatial reasoning, and attention. We report results from 45 participants aged 19 to 63 years who completed a two-hour battery comprising four different cognitive tasks. Subjective fatigue ratings and task performance were measured at the beginning and end of the battery. Our novel method resulted in an increase in subjective ratings of fatigue (p < 0.001) and a reduction in task performance (p = 0.008). Future research into mental fatigue may benefit from using this task battery.

15.
Curr Issues Mol Biol ; 45(7): 5879-5901, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37504288

ABSTRACT

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The molecular dynamics simulation using Desmond and the normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein's receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization, and their expressional profile in different tissues was studied. These in silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

16.
Cells ; 12(10)2023 05 18.
Article in English | MEDLINE | ID: mdl-37408257

ABSTRACT

Heavy ethanol consumption during adolescence has been linked to neuroimmune response dysregulation and cognitive deficits in the developing adolescent brain. During adolescence, the brain is particularly susceptible to the pharmacological effects of ethanol that are induced by acute and chronic bouts of exposure. Numerous preclinical rodent model studies have used different ethanol administration techniques, such as intragastric gavage, self-administration, vapor, intraperitoneal, and free access, and while most models indicated proinflammatory neuroimmune responses in the adolescent brain, there are various factors that appear to influence this observation. This review synthesizes the most recent findings of the effects of adolescent alcohol use on toll-like receptors, cytokines, and chemokines, as well as the activation of astrocytes and microglia with an emphasis on differences associated with the duration of ethanol exposure (acute vs. chronic), the amount of exposure (e.g., dose or blood ethanol concentrations), sex differences, and the timing of the neuroimmune observation (immediate vs. persistent). Finally, this review discusses new therapeutics and interventions that may ameliorate the dysregulation of neuroimmune maladaptations after ethanol exposure.


Subject(s)
Brain , Ethanol , Female , Male , Animals , Ethanol/pharmacology , Toll-Like Receptors , Cytokines/pharmacology , Microglia
17.
SAGE Open Med ; 11: 20503121231187736, 2023.
Article in English | MEDLINE | ID: mdl-37489137

ABSTRACT

Objective: The continuing COVID-19 pandemic is a coronavirus-related health emergency (severe acute respiratory syndrome coronavirus 2). Inadequate efforts are still being made to address the illness situation in Libya, and this must change. To address these issues, we looked into the demography and trend of the disease as well as the potential risk factors for infection. Methods: This study is a retrospective case-control study conducted online among 616 COVID-19 patients. The p0.05 value, odds ratios, and 95% confidence intervals were calculated and analyzed from the drawn data. Results: Males were at high risk of COVID-19 than females (odds ratio = 1.3, 95% confidence interval: 1.042-1.622; p = 0.02). Anosmia and ageusia were more prominent in females. Patients with an "AB" blood group are significantly susceptible to infection. Adults (31 and above) are highly liable to infection. The univariate logistic regression analysis revealed that smoking is a risk factor for those above 60 years (odds ratio = 2.228, 95% confidence interval: 1.145-4.336; p = 0.018). Individuals with chronic diseases such as diabetes and/or hypertension are more prone to COVID-19 (odds ratio = 10.045, 95% confidence interval: 3.078-32.794; p = 0.000 and odds ratio = 11.508, 95% confidence interval: 3.930-33.695; p = 0.000, respectively). Conclusion: This study provided for the first time the demographic data and the trend of COVID-19 infection in Libya, which will assist the stakeholders and governmental bodies in planning protection strategies against the pandemic.

18.
Int J Antimicrob Agents ; 62(3): 106906, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37392947

ABSTRACT

INTRODUCTION AND OBJECTIVES: The emergence of Candida auris has created a global health challenge. Azole antifungals are the most affected antifungal class because of the extraordinary capability of C. auris to develop resistance against these drugs. Here, we used a combinatorial therapeutic approach to sensitize C. auris to azole antifungals. METHODS AND RESULTS: We have demonstrated the capability of the HIV protease inhibitors lopinavir and ritonavir, at clinically relevant concentrations, to be used with azole antifungals to treat C. auris infections both in vitro and in vivo. Both lopinavir and ritonavir exhibited potent synergistic interactions with the azole antifungals, particularly with itraconazole against 24/24 (100%) and 31/34 (91%) of tested C. auris isolates, respectively. Furthermore, ritonavir significantly interfered with the fungal efflux pump, resulting in a significant increase in Nile red fluorescence by 44%. In a mouse model of C. auris systemic infection, ritonavir boosted the activity of lopinavir to work synergistically with fluconazole and itraconazole and significantly reduced the kidney fungal burden by a 1.2 log (∼94%) and 1.6 log (∼97%) CFU, respectively. CONCLUSION: Our results urge further comprehensive assessment of azoles and HIV protease inhibitors as a novel drug regimen for the treatment of serious invasive C. auris infections.


Subject(s)
Candidiasis , HIV Protease Inhibitors , Animals , Mice , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Ritonavir/therapeutic use , Azoles/pharmacology , Azoles/therapeutic use , Itraconazole/pharmacology , Itraconazole/therapeutic use , Lopinavir/pharmacology , Lopinavir/therapeutic use , Candida auris , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , Candidiasis/drug therapy , Candidiasis/microbiology , Microbial Sensitivity Tests , Drug Resistance, Fungal
19.
Anal Chem ; 95(26): 9901-9913, 2023 07 04.
Article in English | MEDLINE | ID: mdl-37310727

ABSTRACT

Candida albicans (C. albicans), a major fungal pathogen, causes life-threatening infections in immunocompromised individuals. Fluconazole (FLC) is recommended as first-line therapy for treatment of invasive fungal infections. However, the widespread use of FLC has resulted in increased antifungal resistance among different strains of Candida, especially C. albicans, which is a leading source of hospital-acquired infections. Here, by hyperspectral stimulated Raman scattering imaging of single fungal cells in the fingerprint window and pixel-wise spectral unmixing, we report aberrant ergosteryl ester accumulation in azole-resistant C. albicans compared to azole-susceptible species. This accumulation was a consequence of de novo lipogenesis. Lipid profiling by mass spectroscopy identified ergosterol oleate to be the major species stored in azole-resistant C. albicans. Blocking ergosterol esterification by oleate and suppressing sterol synthesis by FLC synergistically suppressed the viability of C. albicans in vitro and limited the growth of biofilm on mouse skin in vivo. Our findings highlight a metabolic marker and a new therapeutic strategy for targeting azole-resistant C. albicans by interrupting the esterified ergosterol biosynthetic pathway.


Subject(s)
Antifungal Agents , Candida albicans , Animals , Mice , Antifungal Agents/chemistry , Azoles/pharmacology , Azoles/metabolism , Spectrum Analysis, Raman , Esters/metabolism , Oleic Acid/metabolism , Microbial Sensitivity Tests , Fluconazole/metabolism , Ergosterol/pharmacology , Ergosterol/metabolism
20.
Polymers (Basel) ; 15(11)2023 May 24.
Article in English | MEDLINE | ID: mdl-37299229

ABSTRACT

Molybdenum carbide co-catalyst and carbon nanofiber matrix are suggested to improve the nickel activity toward methanol electrooxidation process. The proposed electrocatalyst has been synthesized by calcination electrospun nanofiber mats composed of molybdenum chloride, nickel acetate, and poly (vinyl alcohol) under vacuum at elevated temperatures. The fabricated catalyst has been characterized using XRD, SEM, and TEM analysis. The electrochemical measurements demonstrated that the fabricated composite acquired specific activity for methanol electrooxidation when molybdenum content and calcination temperature were tuned. In terms of the current density, the highest performance is attributed to the nanofibers obtained from electrospun solution having 5% molybdenum precursor compared to nickel acetate as a current density of 107 mA/cm2 was generated. The process operating parameters have been optimized and expressed mathematically using the Taguchi robust design method. Experimental design has been employed in investigating the key operating parameters of methanol electrooxidation reaction to obtain the highest oxidation current density peak. The main effective operating parameters of the methanol oxidation reaction are Mo content in the electrocatalyst, methanol concentration, and reaction temperature. Employing Taguchi's robust design helped to capture the optimum conditions yielding the maximum current density. The calculations revealed that the optimum parameters are as follows: Mo content, 5 wt.%; methanol concentration, 2.65 M; and reaction temperature, 50 °C. A mathematical model has been statistically derived to describe the experimental data adequately with an R2 value of 0. 979. The optimization process indicated that the maximum current density can be identified statistically at 5% Mo, 2.0 M methanol concentration, and 45 °C operating temperature.

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