New Natural Eugenol Derivatives as Antiproliferative Agents: Synthesis, Biological Evaluation, and Computational Studies.

Semisynthetic modifications of natural products have bestowed us with many anticancer drugs. In the present work, a natural product, eugenol, has been modified synthetically to generate new anticancer agents. The final compounds were structurally confirmed by NMR, IR, and mass techniques. From the cytotoxicity results, compound 17 bearing morpholine was found to be the most active cytotoxic agent with IC50 1.71 (MCF-7), 1.84 (SKOV3), and 1.1 µM (PC-3) and a thymidylate synthase (TS) inhibitor with an IC50 of 0.81 µM. Further cellular studies showed that compound 17 could induce apoptosis and arrest the cell cycle at the S phase in PC-3 carcinoma. The docking study strongly favors compound 17 to be a TS inhibitor as it displayed a similar interaction to 5-fluorouracil. The in silico pharmacokinetics and DFT computational studies support the results obtained from docking and biological evaluation and displayed favorable pharmacokinetic profile for a drug to be orally available. Compound 17 was found to be a promising TS inhibitor which could suppress DNA synthesis and consequently DNA damage in prostate cancer cells.

Middle eastern college of obstetricians and gynecologists (MCOG) practice guidelines: Role of prediction models in management of trial of labor after cesarean section. Practice guideline no. 05-O-22✰,✰✰,☠,☠☠.

Cesarean delivery rates have been steadily rising since the beginning of the 21st century. The growing incidence is even more prominent in developing countries owing to lack of evidence-based guidance and audit, and the expansion of private practice. The uprise in Cesarean delivery rate has been associated with considerable financial burden and has increased the risk otherwise uncommon serious complications such as placenta accreta disorders and uterine rupture. In addition to primary prevention of Cesarean delivery, trial of labor after cesarean section is one of the most successful strategies to reduce Cesarean deliveries and minimize risks associated with higher order Cesarean deliveries. This guideline appraises patient selection strategies and use of prediction model to promote counseling and enhance safety in women considering vaginal birth after Cesarean.

An off-the-shelf otoacoustic-emission probe for hearing screening via a smartphone.

Otoacoustic emissions (OAEs) provide information about the function of the outer hair cells of the cochlea. In high-income countries, infants undergo OAE tests as part of the screening protocols for hearing. However, the cost of the necessary equipment hinders early screening for hearing in low- and middle-income countries, which disproportionately bear the brunt of disabling hearing loss. Here we report the design and clinical testing of a low-cost probe for OAEs. The device, which has a material cost of approximately US$10, uses an off-the-shelf microphone and off-the-shelf earphones connected to a smartphone through a headphone jack. It sends two pure tones through each of the headphone's earbuds and algorithmically detects the distortion-product OAEs generated by the cochlea and recorded via the microphone. In a clinical study involving 201 paediatric ears across three healthcare sites, the device detected hearing loss with 100% sensitivity and 88.9% specificity, comparable to the performance of a commercial device. Low-cost devices for OAE testing may aid the early detection of hearing loss in resource-constrained settings.

Comparison of Chlorhexidine and Hydrogen Peroxide as Preprocedural Mouthrinse during Ultrasonic Scaling: A Triple-Blinded Randomized Controlled Clinical Trial.

Background: Every year, around 2 million people suffer from hospital-acquired infections worldwide. Aerosols are produced while performing ultrasonic scaling. They are potential source of infection and cross contamination. It can result in spread of several infections including hepatitis, HIV, SARS CoV 2, etc. Preprocedural rinse before scaling is considered an effective measure to reduce the microbial load in aerosols. Materials and Methods: This study was a triple-blinded randomized controlled trial performed on 90 participants diagnosed with chronic periodontitis. Random allocation of participants into three groups, i.e., Group-1, Group-2, and Group-3, was done, wherein 0.12% chlorhexidine (CHX), 1.5% hydrogen peroxide (HP), and distilled water (DW) were used, respectively, as preprocedural mouthrinse. The participants of each group were instructed to perform mouthrinse for 60 s before the start of ultrasonic scaling sessions. Blood agar plates were kept at three locations, i.e., operator's chest area, patient's chest area, and assistant's chest area for aerosol collection after scaling. Colony-forming units (CFUs) were counted for microbiological analysis. Results: Least number of CFUs was found in the CHX group, followed by HP and DW groups. Location wise, the patient's chest area had the highest CFU count and the least was at the assistant's chest area. CFU count between the groups was statistically significant. Conclusion: Preprocedural rinse using HP can effectively be used as a method to reduce dental aerosols generated during ultrasonic scaling.

Variation of Aflatoxin Levels in Stored Edible Seed and Oil Samples and Risk Assessment in the Local Population.

Five hundred and twenty samples of edible seeds and oilseeds (sunflower, palm, peanut, sesame, cotton, and grapeseed) were purchased from markets, farmers, and superstores in the central cities of Punjab, Pakistan. A total of 125 (48.1%) edible seed samples from a 6 ≤ months storage period, and 127 (48.8%) from a 2 ≥ years storage period were found to be infested with AFs. The average elevated amount of AFB1 and total AFs was observed in a 2 ≥ years storage period, i.e., 28.6 ± 4.5 and 51.3 ± 10.4 µg/kg, respectively, in sesame seeds. The minimum amount of AFB1 and total AFs was observed in palm seed samples with a storage period of 6 ≤ months, i.e., 9.96 ± 2.4, and 11.7 ± 1.90 µg/kg, respectively. The maximum amount of AFB1 and total AFs were observed in peanut oil samples, i.e., 21.43 ± 2.60 and 25.96 ± 4.30 µg/kg, respectively, with a storage period of 2 ≥ years. Therefore, the maximum dietary intake of 59.60 ng/kg/day was observed in oil samples stored at a ≥ 2 years storage period. The results of the present study concluded that a significant difference was found in the amounts of total AFs in edible seed samples stored at 6 ≤ months and 2 ≥ years storage periods (p < 0.05).

Theragnostic Applications of Mammal and Plant-Derived Extracellular Vesicles: Latest Findings, Current Technologies, and Prospects.

The way cells communicate is not fully understood. However, it is well-known that extracellular vesicles (EVs) are involved. Researchers initially thought that EVs were used by cells to remove cellular waste. It is now clear that EVs function as signaling molecules released by cells to communicate with one another, carrying a cargo representing the mother cell. Furthermore, these EVs can be found in all biological fluids, making them the perfect non-invasive diagnostic tool, as their cargo causes functional changes in the cells upon receiving, unlike synthetic drug carriers. EVs last longer in circulation and instigate minor immune responses, making them the perfect drug carrier. This review sheds light on the latest development in EVs isolation, characterization and, application as therapeutic cargo, novel drug loading techniques, and diagnostic tools. We also address the advancement in plant-derived EVs, their characteristics, and applications; since plant-derived EVs only recently gained focus, we listed the latest findings. Although there is much more to learn about, EV is a wide field of research; what scientists have discovered so far is fascinating. This paper is suitable for those new to the field seeking to understand EVs and those already familiar with it but wanting to review the latest findings.

Pro-Neurotensin as a Potential Novel Diagnostic Biomarker for Detection of Nonalcoholic Fatty Liver Disease.

Background and Aims: Currently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case-control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases. Methods: Clinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs-122 and pro-neurotensin. Results: Compared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p<0.001) and at a cut-off ≥6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥108. Conclusion: The circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH.

Untargeted Metabolomics Identifies a Novel Panel of Markers for Autologous Blood Transfusion.

Untargeted metabolomics was used to analyze serum and urine samples for biomarkers of autologous blood transfusion (ABT). Red blood cell concentrates from donated blood were stored for 35−36 days prior to reinfusion into the donors. Participants were sampled at different time points post-donation and up to 7 days post-transfusion. Metabolomic profiling was performed using ACQUITY ultra performance liquid chromatography (UPLC), Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The markers of ABT were determined by principal component analysis and metabolites that had p < 0.05 and met ≥ 2-fold change from baseline were selected. A total of 11 serum and eight urinary metabolites, including two urinary plasticizer metabolites, were altered during the study. By the seventh day post-transfusion, the plasticizers had returned to baseline, while changes in nine other metabolites (seven serum and two urinary) remained. Five of these metabolites (serum inosine, guanosine and sphinganine and urinary isocitrate and erythronate) were upregulated, while serum glycourdeoxycholate, S-allylcysteine, 17-alphahydroxypregnenalone 3 and Glutamine conjugate of C6H10O2 (2)* were downregulated. This is the first study to identify a panel of metabolites, from serum and urine, as markers of ABT. Once independently validated, it could be universally adopted to detect ABT.

Influence of Oral Dipping Tombak Smokeless Tobacco on Coagulation Profile and Platelet Counts.

The goal of this paper is to investigate the influence of oral dipping of Tombak Smokeless Tobacco (SLT) on prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio(INR) values, and platelet counts (PLTs), in Sudanese Tombak users. An analytical cross-sectional study was conducted at Kosti health insurance hospital, Sudan, in 2019. According to the inclusion and exclusion criteria, 100 adult users of oral Tombak for three or more years were chosen randomly as a study group. Another 100 matched healthy individuals who never used Tombak were randomly selected as a comparative group. Venous blood specimens were collected in ethylene diamine tetra-acetic acid (EDTA) containers for the PLT counts using the automated haematology analyser (Sysmex, Tokyo, Japan XK-21SYSMEX) and in trisodium citrate anti-coagulant containers for coagulation tests using a co-agulometer machine analyser. Our findings show a significant decrease in PLT count mean values in the Tombak users group (212.1 × 103/mm3 ± 74.3 × 103/mm3) compared with the non-taking Tombak group mean values (243.2 × 103/mm3 ± 83.0 × 103/mm3), (p < 0.006). Both PT and APTT were significantly prolonged in Tombak users (16.03 ± 1.22 s vs. 14.44 ± 0.557 s), p < 0.001 for PT, and (41.62 ± 7.28 s vs. 34.99 ± 4.02 s), (p < 0.001) for APTT. INR mean values were significantly longer in Tombak users (1.11 ± 0.096) vs. (1.07 ± 0.66; p < 0.001). Multiple linear regression analysis findings show a significant impact of the four investigated variables, including duration of taking Tombak, age, and frequency of taking Tombak per day (p < 0.001). In conclusion, using Tombak a Smokeless Tobacco (SLT) for a long period significantly affect Platelet counts and coagulation profile.

Meary angle for the prediction of mitral valve prolapse risk in non-syndromic patients with pes planus, a cross-sectional study.

OBJECTIVES: Mitral Valve Prolapse (MVP) is a common valvular abnormality accounting for 2% of the population. There is a reported association between pes planus (PP) and MVP in some syndromes such as Marfan. However, this association has not been tested in non-syndromic cases. The primary outcome of this study is to measure the prevalence of MVP in a population of patients with PP. The secondary outcome parameter is to determine if the Meary angle (MA), a measure of the severity of flat foot, can be effectively used in the prediction of the presence of MVP. Forty-one patients with PP were screened using a lateral x-ray foot to determine MA while echocardiography was utilized to identify the presence and grade of MVP. RESULTS: 88% of screened patients were diagnosed with MVP. MA was correlated with the grade of MVP and showed high diagnostic accuracy (sensitivity 100% and specificity 90%) in predicting MVP risk when higher than 5. Children with PP are at a higher risk for MVP than the general population. Accordingly, the utilization of MA in such a specific population for the determination of patients at a higher need for echocardiography seems to be a worthwhile strategy in diagnosing MVP.

ZnO Nanocomposites of Juniperus procera and Dodonaea viscosa Extracts as Antiproliferative and Antimicrobial Agents.

Cancer and microbial infections constitute a major burden and leading cause of death globally. The development of therapeutic compounds from natural products is considered a cornerstone in drug discovery. Therefore, in the present study, the ethanolic extract and the fractions of Dodonaea viscosa and Juniperus procera were evaluated for anticancer and antimicrobial activities. It was found that two fractions, JM and DC, exhibited promising anticancer and antimicrobial activities. The JM and DC fractions were further modified into ZnO nanocomposites, which were characterized by SEM, XRD, TGA, and EDX. It was noted that the synthesized nanocomposites displayed remarkable enhancement in cytotoxicity as well as antibacterial activity. Nanocomposite DC-ZnO NRs exhibited cytotoxicity with IC50 values of 16.4 ± 4 (HepG2) and 29.07 ± 2.7 µg/mL (HCT-116) and JM-ZnO NRs with IC50 values of 12.2 ± 10.27 (HepG2) and 24.1 ± 3.0 µg/mL (HCT-116). In addition, nanocomposites of DC (i.e., DC-ZnO NRs) and JM (i.e., JM-ZnO NRs) displayed excellent antimicrobial activity against Staphylococcus aureus with MICs of 2.5 and 1.25 µg/mL, respectively. Moreover, these fractions and nanocomposites were tested for cytotoxicity against normal fibroblasts and were found to be non-toxic. GC-MS analysis of the active fractions were also carried out to discover the possible phytochemicals that are responsible for these activities.

Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1, and MAPK/NF-κB signaling pathways.

This study investigated the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA) - induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA), increased renal levels of superoxide dismutase (SOD), and reversed the increase of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) caused by TAA. Taurine treatment also led to a significant rise in nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) levels, with significant suppression of extracellular signal-regulated kinase (ERK) 1/2, nuclear factor kappa B (NF-κB), and tumor necrosis factor α (TNF-α) gene expressions, and interleukin-18 (IL-18) and TNF-α protein levels compared with those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its antioxidant and anti-inflammatory effects. Taurine antioxidant activity is accredited for its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation.

Efficacy of Preprocedural Boric Acid Mouthrinse in Reducing Viable Bacteria in Dental Aerosols Produced during Ultrasonic Scaling.

INTRODUCTION: Aerosols and droplets contaminated with bacteria and blood are produced during ultrasonic scaling. Measures to control aerosol contamination in dental clinics are recommended by the Centers for Disease Control and Prevention. This study aimed to evaluate the efficacy of preprocedural boric acid (BA) mouthrinse in reducing bacterial contamination in dental aerosols generated during ultrasonic scaling. MATERIALS AND METHODS: This was a randomised clinical trial in 90 systemically healthy subjects (25-55 yrs) diagnosed with chronic periodontitis who were allocated into three groups of 30 subjects each to receive, Group A - 0.12% chlorhexidine (CHX), Group B - 0.75% BA and Group C-water, as a preprocedural rinse for 1 min. The aerosol generated while performing ultrasonic scaling for 30 min was collected at three locations on blood agar plates. Incubation of the blood agar plates at 37°C for next 48 h for aerobic culture was performed and subsequently colony-forming units (CFUs) were counted. RESULTS: CFUs in Group A were significantly reduced compared with Group B (P < 0.001). When we compare CFUs in all the three groups, CFUs in Groups A and B were statistically significantly reduced compared with Group C (P < 0.001). Furthermore, it was also observed that the assistant's chest area had lowest CFUs whereas patient's chest area had highest. CONCLUSION: This study recommends routine use of preprocedural mouthrinse as a measure to reduce bacterial aerosols generated during ultrasonic scaling and that 0.12% CHX gluconate is more effective than 0.75% BA mouthwash in reducing CFUs count.

Periodontitis and diabetes mellitus co-morbidity: A molecular dialogue.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and periodontitis are two biologically linked diseases that often coexist in complex interaction. While periodontitis may lead to insulin receptor desensitization, diabetes may increase the expression of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin 6 (IL-6), in the gingival crevicular fluid and activate osteoclasts via Receptor activator of nuclear factor kappa-Β ligand (RANK-L) production, leading to bone resorption. However, the association between the two diseases processes, where one may exacerbate the progression of the other, is unclear. In addition, both diseases have similar mechanistic themes, such as chronic inflammation and oxidative stress. This review aimed to investigate the pathophysiological and molecular mechanisms underlying T2DM and periodontitis. HIGHLIGHT: Uncontrolled diabetes is often associated with severe periodontitis, measured by clinical attachment loss. Alteration in the oral microbiome composition, which may activate the host inflammatory response and lead to irreversible oxidative stress, is a common finding in both diseases. An understanding of the molecular crosstalk between the two disease processes is crucial for developing therapeutic targets that inhibit bone resorption and halt the progression of periodontitis in patients with diabetes. CONCLUSION: The Oral microbiome composition in T2DM and periodontitis shifts toward dysbiosis, favoring bacterial pathogens, such as Fusobacteria and Porphyromonas species. Both conditions are marked by pro-inflammatory immune activity via the activation of Interleukin 17 (IL-17), Interleukin 1 (IL-1), TNF-α, and Nuclear Factor Kappa Beta (NF-κB). Common molecular crosstalk signaling appears to involve advanced glycation end products (AGEs) and oxidative stress. Thus, future drug targets are multifactorial, ranging from modulatory of host inflammatory response to preventing the accumulation of AGEs and oxidative free radicals.

Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents.

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6-18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC50 1.1 µM), HCT-116 (IC50 2.6 µM), and HepG2 (IC50 1.4 µM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC50 in the range 1.95-4.24 µM, whereas the standard drug, Pemetrexed, showed IC50 7.26 µM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential.

Occurrence of Aflatoxins in Edible Vegetable Seeds and Oil Samples Available in Pakistani Retail Markets and Estimation of Dietary Intake in Consumers.

Aflatoxins (AFs) are secondary metabolites toxic to humans as well as animals. The environmental conditions, conventional agricultural practices, and illiteracy are the main factors which favor the production of AFs in food and feed. In the current study 744 samples of vegetable seeds and oils (soybean, sunflower, canola, olive, corn, and mustard) were collected and tested for the presence of aflatoxin B1 (AFB1) and total AFs. Liquid-liquid extraction was employed for the extraction of AFs from seeds and oil samples. Reverse phase high performance liquid chromatography equipped with fluorescence detection was used for the analysis. The results have shown that 92 (56.7%) samples of imported and 108 (57.0%) samples of local edible seeds were observed to be contaminated with AFs. All samples of edible seeds have AFB1 levels greater than the proposed limit set by the European Union (EU, 2 µg/kg) and 12 (7.40%) samples of imported seeds and 14 (7.40%) samples of local seeds were found in the range ≥ 50 µg/kg. About 78 (43.3%) samples of imported edible oil and 103 (48.3%) sample of local edible oil were observed to be positive for AFs. Furthermore, 16 (8.88%) and six (3.33%) samples of imported vegetable oil have levels of total AFs in a range (21-50 µg/kg) and greater than 50 µg/kg, respectively. The findings indicate significant differences in AFs levels between imported and local vegetable oil samples (t = 22.27 and p = 0.009) at α = 0.05 and a significant difference in AFs levels were found between vegetable seeds and oil samples (t = -17.75, p = 0.009) at α = 0.05. The highest dietary intake was found for a local sunflower oil sample (0.90 µg/kg/day) in female individuals (16-22 age group). The results have shown considerably high levels of AFB1 and total AFs in seeds and oil samples and emphasise the need to monitor carefully the levels of these toxic substances in food and feed on regular basis.

Hematological indices and abnormalities among patients with uncomplicated falciparum malaria in Kosti city of the White Nile state, Sudan: a comparative study.

BACKGROUND: Hematological abnormalities are common features in falciparum malaria but vary among different populations across countries. Therefore, we compared hematological indices and abnormalities between Plasmodium falciparum-infected patients and malaria-negative subjects in Kosti city of the White Nile State, Sudan. METHODS: A comparative, cross-sectional study was conducted at the Clinical Laboratory Unit of Kosti Teaching Hospital from June to December 2018. A total of 392 participants (192 P. falciparum-infected patients and 200 malaria-negative subjects) were recruited in the study. Hematological indices of hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets were measured, and their median values were statistically compared. RESULTS: The majority of P. falciparum-infected patients (67.6%) showed a low-level parasitemia. The median values of Hb concentration, RBC count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were significantly lower in P. falciparum-infected patients, while the median red cell distribution width (RDW) was significantly higher in the patients compared to malaria-negative subjects. Anemia, low MCV, low MCH, low MCHC and high RDW were significantly associated with falciparum malaria, but parasitemia level was not significantly associated with anemia severity. The median total WBC count was non-significantly higher in P. falciparum-infected patients, with neutropenia being significantly associated with falciparum malaria. The median platelet count was significantly lower in P. falciparum-infected patients, with thrombocytopenia being significantly associated with falciparum malaria. CONCLUSIONS: Falciparum malaria among patients in Kosti city of the White Nile State, Sudan is predominantly of low-level parasitemia. It is significantly associated with anemia, low MCV, low MCH, low MCHC, high RDW, thrombocytopenia and neutropenia. However, parasitemia level is not a significant predictor of anemia severity. On the other hand, leucopenia is not useful to predict falciparum malaria. Further large-scale studies in community and healthcare settings and inclusion of patients with complicated or severe malaria and those with high parasite densities are recommended.

PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: a review of literature.

BACKGROUND: Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. SHORT CONCLUSION: In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.

Variation of Deoxynivalenol Levels in Corn and Its Products Available in Retail Markets of Punjab, Pakistan, and Estimation of Risk Assessment.

This study investigated the natural incidence of deoxynivalenol (DON) in corn and corn products from corn-producing districts of Punjab, Pakistan. The analysis was carried out using high performance liquid chromatography (HPLC) with UV detector and immunoaffinity cleanup columns. The detection limit (LOD) and limit of quantification were 25 and 50 µg/kg, respectively. A total of 1220 samples of corn and corn products were analyzed to detect DON, and 539 (44.2%) samples were observed to be contaminated with DON (n ≥ LOD). Furthermore, 92 (7.5%) samples of corn and corn products had DON levels that were higher than the proposed limits of the EU. The data are significantly different from a normal distribution of DON in samples of corn and corn products from different locations (p < 0.05) for Shapiro-Wilk and Kolmogorov-Smirnov values. However, a significant difference in DON levels was found between corn and corn-derived products (p ≤ 0.05). The lowest and highest exposures, and hazard quotient (HQ) values of 0.92 and 9.68 µg/kg bw/day, were documented in corn flour samples.

Patulin Contamination of Citrus Fruits from Punjab and Northern Pakistan and Estimation of Associated Dietary Intake.

This research aims to assess the natural occurrence of patulin (PAT) in selected citrus fruits from central cities of Punjab and Pakistan's northern cities. A total of 2970 fruit samples from 12 citrus cultivars were examined using liquid chromatography fitted with a UV detector. The detection limit (LOD) and quantification limit were 0.04 and 0.12 µg/kg, respectively. About 56% of samples of citrus fruits from Punjab's central cities, Pakistan, were found to be contaminated with PAT, with values ranging from 0.12 to 1150 µg/kg in samples from central Punjab cities. Furthermore, 31.7% of samples of citrus fruits from northern cities of Pakistan were contaminated with PAT, with values ranging from 0.12 to 320 µg/kg. About 22.1% of citrus fruit samples had PAT levels greater than the suggested limits established by the European Union (EU). The dietary intake levels of PAT ranged from 0.10 to 1.11 µg/kg bw/day in the central cities of Punjab, Pakistan, and 0.13 to 1.93 µg/kg bw/day in the northern cities of Pakistan.