Synthesis, biochemical characterization and in silico investigation of 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid derivatives: dual action mode inhibitors of urease and virulent bacterial stains.

In the present work, we reported the synthesis of Schiff bases from 4-phenoxy-5-sulfamoylbenzoic acid motif. The reaction was carried out by substitution of different aldehyde and ketones at sulfamoyl group of sulfamoylbenzoic acid. The generated substituted products (4a-4i) possessed potent structure activity relationship and exhibited drug like properties. The structures of synthesized compounds were characterized on the basis of FT-IR, 1H NMR, 13C NMR and mass spectroscopic data. The effects of synthesized products were investigated on urease enzyme through anti-urease enzyme inhibition assay (Weather burn method). These compounds were further evaluated for antibacterial potential. The Rationale behind the assessment of antibacterial activity was to investigate the synthesized compound's dual mode action against urease and virulent bacterial strains in order to develop a lead candidate for the treatment of GIT diseases such as gastric and peptic ulcers, as well as hepatic encephalopathy. The synthesized derivatives have outstanding anti-urease and antibacterial action, as is evident from in vitro and in silico studies. As a result, these compounds (3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid; 4a-4i) might be explored further as a potential lead for the development of potent inhibitors in the future.

Computational Exploration of Fluorocyclopentenyl-purines and-pyrimidines Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor (EGFR) for the Treatment of Breast Cancer.

The Epidermal Growth Factor Receptor (EGFR) is an important therapeutic target for the treatment of a variety of epithelial malignancies, including breast cancer, in which EGFR is aberrantly expressed.The fluorocyclopentenyl-purine-pyrimidines derivatives, which have previously been described as powerful compounds against breast cancer, were selected to investigate their potential against EGFR using computational tools in an effort to obtain potent inhibitors with fewer adverse effects. The molecule's chemical reactivity and stability were assessed by determining the HOMO-LUMO energy gap using density functional theory (DFT) calculations. Among all the selected compounds, PU4 displayed a HOMO-LUMO gap of 0.191 eV. Additionally, molecular docking analysis was performed to assess the binding affinities of PU4 within the active pocket of EGFR-TK. The compound PU4 showed potent interactions with EGFR exhibiting -32.3 kJ/mol binding energy which was found best as compared to gefitinib i. e., -27.4 kJ/mol which was further validated by molecular dynamics simulations and ADMET analysis. The results of these analyses indicate that the top hits obtained from the virtual screening possess the ability to act as effective EGFR inhibitor. Therefore, it is recommended to further investigate the inhibitory potential of these identified compounds using in vitro and in vivo approaches.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Low-Frequency Oscillations in Optical Measurements of Metal-Nanoparticle Vibrations.

Time-resolved optical measurements of vibrating metal nanoparticles have been used extensively to probe the ultrafast mechanical properties of the nanoparticles and of the surrounding liquid, but nearly all investigations so far have been limited to the linear regime. Here, we report the observation of a low-frequency oscillating signal in transient-absorption measurements of nanoparticles with octahedral gold cores and cubic silver shells; the signal appears at the difference of two mechanical vibrational frequencies in the particles, suggesting a nonlinear mixing process. We tentatively attribute this proposed mixing to a nonlinear coupling between a vibrational mode of the nanoparticle and its optical-frequency plasmon resonance. The optimization of this nonlinear transduction may enable high-efficiency opto-mechanical frequency mixing in the GHz-THz frequency regime.

Prenatal diagnosis of maternal serum from mothers carrying ß-thalassemic fetus.

BACKGROUND: This study focuses on the discovery of protein biomarkers from the maternal serum of ß-thalassemic trait mothers carrying the normal fetus and ß-thalassemic major fetus. METHODS: Serum samples from ß-thalassemic trait mothers carrying major (N = 5) and normal fetuses (N = 5) were studied. The IVS1-5 thalassemia mutation was common among ß-thalassemic trait mothers who were carrying a homozygous ß-thalassemic fetus (IVS1-5/ IVS1-5 mutation) or a normal fetus (no mutation). We employed two-dimensional gel electrophoresis and mass spectrometry analysis to explore differentially expressed maternal serum proteins from thalassemia carrier couples with the same ß-thalassemia mutation. Western blotting was performed for one of the identified proteins to validate our data. RESULTS: Ten proteins were identified in the maternal serum of ß-thalassemic trait mothers carrying the ß-thalassemic major fetus and normal fetus. Among these, serotransferrin, haptoglobin, α-1 anti-trypsin, apo-lipoprotein A1, and the fibrinogen-ß chain were found to be upregulated in mothers carrying major fetuses and are known to be associated with pregnancy-related disorders. The expression of α-1 anti-trypsin was validated through western blotting. CONCLUSIONS: Proteins identified in the current study from maternal serum are reported to contribute to hereditary disorders. We suggest that these can serve as putative screening markers for non-invasive prenatal diagnosis in ß-thalassemic pregnancies.

Exploring 2-Tetradecanoylimino-3-aryl-4-methyl-1,3-thiazolines Derivatives as Alkaline Phosphatase Inhibitors: Biochemical Evaluation and Computational Analysis.

The current study focused on the laboratory approach in conjunction with computational methods for the synthesis and bioactivity assessment of unique 2-tetradecanoylimino-3-aryl-4-methyl-1,3-thiazolines (2a-2k). Processes included cyclizing 1-aroyl-3-arylthioureas with propan-2-one in the presence of trimethylamine and bromine. By using spectroscopic techniques and elemental analyses, structures were elucidated. To assess the electronic properties, density functional theory (DFT) calculations were made, while binding interactions of synthesized derivatives were studied by the molecular docking tool. Promising results were found during the evaluation of bioactivity of synthesized compounds against alkaline phosphatase. The drug likeliness score, an indicator used for any chemical entity posing as a drug, was within acceptable limits. The data suggested that most of the derivatives were potent inhibitors of alkaline phosphatase, which in turn may act as lead molecules to synthesize derivatives having desired pharmacological profiles for the treatment of specific diseases associated with abnormal levels of ALPs.

Interparticle gap geometry effects on chiroptical properties of plasmonic nanoparticle assemblies.

Chiral linear assemblies of plasmonic nanoparticles with chiral optical activity often show low asymmetry factors. Systematic understanding of the structure-property relationship in these systems must be improved to facilitate rational design of their chiroptical response. Here we study the effect of large area interparticle gaps in chiral linear nanoparticle assemblies on their chiroptical properties using a tetrahelix structure formed by a linear face-to-face assembly of nanoscale Au tetrahedra. Using finite-difference time-domain and finite element methods, we performed in-depth evaluation of the extinction spectra and electric field distribution in the tetrahelix structure and its dependence on various geometric parameters. The reported structure supports various plasmonic modes, one of which shows a strong incident light handedness selectivity that is associated with large face-to-face junctions. This works highlights the importance of gap engineering in chiral plasmonic assemblies to achieveg-factors greater than 1 and produce structures with a handedness-selective optical response.

Uptake, satisfaction, and quality of family planning services in Pakistan: before and during Covid-19 outbreak: Stocktaking with clients of a private sector organisation.

OBJECTIVE: To report the uptake, satisfaction, and quality of family planning services in the clients of a private sector organisation during Covid-19 in Pakistan and compare it with the situation before Covid-19 pandemic. METHODS: This paper is based on the client exit interview data collected before and then after the outbreak of Covid-19, using a structured questionnaire. Clients were chosen at the exit of the social franchise (SF) clinics, situated in rural and peri-urban areas, and beneficiaries of the outreach services delivery channel in the remote rural area. Descriptive analysis was carried out in SPSS, and frequencies and percentages were computed. RESULTS: All respondents were married women of reproductive age (MWRA) with an average age of 30 years, with either no or very low literacy levels. During the pandemic, overall utilization of the intrauterine contraceptive devices (IUCDs) declined, while the condom remained popular. Client satisfaction remained high in both service delivery channels during a pandemic. However, some results varied vis-à-vis the residence of the client. CONCLUSIONS: All respondents were married women of reproductive age (MWRA) with an average age of 30 years, with either no or very low literacy levels. During the pandemic, overall utilization of the intrauterine contraceptive devices (IUCDs) declined, while the condom remained popular. Client satisfaction remained high in both service delivery channels during a pandemic. However, some results varied vis-à-vis the residence of the client.

Potential preventive and protective perspectives of different spice powders and their mixtures in rat model.

BACKGROUND: The spices based dietary interventions are in lime light among the scientific community owing to their promising therapeutic perspective. The bioactive components in spices can be used to exert various health promoting functions in human body such as prompting weight loss, inhibit diet-induced obesity, hypercholesterolemia, hyperglycemia, allergies and various other maladies. In current study extraction and in vitro characterization of coriander seed (CS), black cumin seed (BCS) and fenugreek seed (FS) polyphenols was conducted for further development of dietary intervention against lipid and glycemia related abnormalities in experimental Sprague Dowley rats fed with control and different spice powder supplemented diets. METHODS: Purposely, extraction of Coriander (CS), Black cumin (BCS) and Fenugreek seeds (FS) were carried out by using water and aqueous methanol (70:30 v/v). Afterwards, the resultant extracts were thoroughly investigated for their antioxidant potential through different indices like TPC, TFC, FRAP and ß Carotene Bleaching Assay and ABTS. Furthermore, HPLC quantification were also conducted with special reference to thymoquinone, disogenin, chlorogenic acid, caffeic acid and kaempferol alongside in vitro pancreatic lipase inhibitory activity estimation. Bio-evaluation trial was consisting of three modules i.e. study-I (normal diet), study-II (high cholesterol diet) and study-III (high sucrose diet). Furthermore, rats were sub-divided in five groups in each module on the basis of diet provision including T0 (control), T1 (Diet containing CS), T2 (Diet containing BCS), T3 (Diet containing FS) and T4 (Diet containing CSP + BCSP + FSP). At the beginning of trial, some rats were dissected to evaluate the baseline values whilst rest of the rats was killed at the termination (56th day). Feed and drink intakes were quantified on daily bases whereas, body weight was calculated weekly. Cholesterol level, serum low density lipoproteins (LDL), high density lipoproteins (HDL), triglycerides, glucose concentration and insulin level of collected sera was measured by standard procedures. RESULTS: The in vitro characterization showed better extraction of spices antioxidant through aqueous methanol as compared to water. Among the spices, Black cumin seed alone or in combination revealed highest antioxidant activity in T2 (BCS) followed by T4 (CS + BCS), T7 (CS + BCS + FS), T1 (CS), T6 (BCS + FS), T5 (CS + FS) and lowest in T3 (FS). Likewise, the HPLC characterization showed the presence of thymoquinone in BCS, Dosignienin FGS and chlorogenic acid, caffeic acid and kaempferol in the other treatments. Furthermore, all the treatments showed dose dependent inhibition in Pancreatic lipase activity and order of inhibition was BCS > CS + BCS > CS + BCS + FS > CS > BCS + FC > CS + FS > FS. The maximum feed intake, drink intake and weight gain was observed in T0 (control) trailed by T1, T2, T3 and T4 group in experimental study I, II and III, respectively. The resultant diet T4 enhanced the high density lipoprotein from T0 (58.58 ± 2.51) to 61.71 ± 1.62 (T4) in hypercholesterolemia rats whereas in hyperglycaemia rats the HDL was varied from 38.77 ± 1.2 to 40.02 ± 0.99 in T0 and T4, respectively. Similarly, T2 significantly lowered the low density lipoprotein from 62.53 ± 1.22 (T1) & 46.53 ± 0.99 to 54.88 ± 0.52 & 40.94 ± 1.99 (T2) in hypercholesteraemic and diabetic rats. Moreover, T4 treatment showed maximum reduction as 10.01 & 11.53% in respective studies. CONCLUSIONS: The diet prepared from the different combination of spices has been proven effective against Oxidative stress related physiological malfunctioning.

High yield expression, characterization, and biological activity of IFNα2-Tα1 fusion protein.

The use of interferon α-2 in combination with thymosin α-1 shows higher anti-cancer effect in comparison when both are used individually because of their synergistic effects. In this study we produced an important human interferon α-2-thymosin α-1 (IFNα2-Tα1) fusion protein with probable pharmaceutical properties coupled to its high-level expression, characterization, and study of its biological activity. The IFNα2-Tα1 fusion gene was constructed by over-lap extension PCR and expressed in Escherichia coli expression system. The expression of IFNα2-Tα1 fusion protein was optimized to higher level and its maximum expression was obtained in modified terrific broth medium when lactose was used as inducer. The fusion protein was refolded into its native biologically active form with maximum yield of 83.14% followed by purification with ∼98% purity and 69% final yield. A band of purified IFNα2-Tα1 fusion protein equal to ∼23 kDa was observed on 12 % SDS-PAGE gel. The integrity of IFNα2-Tα1 fusion protein was confirmed by western blot analysis and secondary structure was assessed by CD spectroscopy. When IFNα2-Tα1 fusion protein was subjected to its biological activity analysis it was observed that it exhibits both IFNα2 & Tα1 activities as well as significantly higher anticancer activity as compared to IFNα-2 alone.

Reconnoitring the impact of different extraction techniques on ginger bioactive moieties extraction, antioxidant characterization and physicochemical properties for their therapeutic effect.

The core directive of current study was to compare the different extraction techniques for their extraction yield of ginger bioactive moieties. Purposely, ultrasonic assisted and supercritical fluid extraction techniques were adapted alongside conventional solvent extraction for comparison. The variables targeted for the extraction process in different modules were time (20, 30, 40 minutes), temperature (30, 40, 50oC), solvent to sample ratio (4:6, 6:4, 8:2), pressure (2000, 3000, 4000 psi) and amplitude (20, 30, 40%). All variables were found to be momentously (P>0.05) effecting the extraction rates. The antioxidant potential of bioactive moieties was evaluated through FRAP, DPPH and ABTS. The outcomes of the optimization process suggested that the total phenolic content and total flavonoids content extracted through 80% ethanol at 50oC for 40 minutes showed maximum antioxidant activity. However, ultrasound assisted extraction, by using 80% ethanol, at 50oC for 40 minutes and at ultrasonic amplitude of 40% exhibited best results. Moreover, supercritical fluid extraction at 50oC for 40 minutes at5000 psi pressure, showed maximum extraction potential. All the extracts gathered through conventional, ultrasound and supercritical techniques were further quantified through HPLC protocols. The statistical interpretation of the results from all the analytical findings revealed highest concentration of polyphenols in supercritical fluids extracts followed by ultrasound and conventional extracts. One best treatment on the basis of superior nutritional profile as depicted by HPLC quantification was selected for the formulation of ginger drink. Physicochemical analysis elucidated momentous upshot on color, pH and acidity with progressive storage period whereas TSS followed a non-significant trend. Moreover, storage interval and treatments significantly affected the antioxidant potential of drinks.

pHLIP peptide targets nanogold particles to tumors.

Progress in nanomedicine depends on the development of nanomaterials and targeted delivery methods. In this work, we describe a method for the preferential targeting of gold nanoparticles to a tumor in a mouse model. The method is based on the use of the pH Low Insertion Peptide (pHLIP), which targets various imaging agents to acidic tumors. We compare tumor targeting by nonfunctionalized nanogold particles with nanogold-pHLIP conjugates, where nanogold is covalently attached to the N terminus of pHLIP. Our most important finding is that both intratumoral and i.v. administration demonstrated a significant enhancement of tumor uptake of gold nanoparticles conjugated with pHLIP. Statistically significant reduction of gold accumulation was observed in acidic tumors and kidney when pH-insensitive K-pHLIP was used as a vehicle, suggesting an important role of pH in the pHLIP-mediated targeting of gold nanoparticles. The pHLIP technology can substantially improve the delivery of gold nanoparticles to tumors by providing specificity of targeting, enhancing local concentration in tumors, and distributing nanoparticles throughout the entire tumor mass where they remain for an extended period (several days), which is beneficial for radiation oncology and imaging.

Engaging with community-based public and private mid-level providers for promoting the use of modern contraceptive methods in rural Pakistan: results from two innovative birth spacing interventions.

BACKGROUND: Family planning (FP) interventions aimed at reducing population growth have negligible during the last two decades in Pakistan. Innovative FP interventions that help reduce the growing population burden are the need of the hour. Marie Stopes Society--Pakistan implemented an operational research project--'Evidence for Innovating to Save Lives', to explore effective and viable intervention models that can promote healthy timing and spacing of pregnancy in rural and under-served communities of Sindh, Punjab and Khyber Pakhtunkhwa provinces of Pakistan. METHODS: We conducted a quasi-experimental (pre- and post-intervention with control arm) study to assess the effectiveness of each of the two intervention models, (1) Suraj model (meaning 'Sun' in English), which uses social franchises (SF) along with a demand-side financing (DSF) approach using free vouchers, and (2) Community Midwife (CMW) model, in promoting the use of modern contraceptive methods compared to respective controls. Baseline and endline cross-sectional household surveys were conducted, 24 months apart, by recruiting 5566 and 6316 married women of reproductive age (MWRA) respectively. We used Stata version 8 to report the net effect of interventions on outcome indicators using difference-in-differences analysis. Multivariate Cox proportional hazard regression analysis was used to assess the net effect of the intervention on current contraceptive use, keeping time constant and adjusting for other variables in the model. RESULTS: The Suraj model was effective in significantly increasing awareness about FP methods among MWRA by 14% percentage points, current contraceptive use by 5% percentage points and long term modern method--intrauterine device (IUD) use by 6% percentage points. The CMW model significantly increased contraceptive awareness by 28% percentage points, ever use of contraceptives by 7% percentage points and, IUD use by 3% percentage points. Additionally the Suraj intervention led to a 35% greater prevalence (prevalence ratio: 1.35, 95% CI: 1.22-1.50) of contraceptive use among MWRA. CONCLUSION: Suraj intervention highlights the importance of embedding subsidized FP services within the communities of the beneficiaries. The outcomes of the CMW intervention also improved the use of long-term contraceptives. These findings indicate the necessity of designing and implementing FP initiatives involving local mid-level providers to expand contraceptive coverage in under-served areas.

Development and validation of a high-performance liquid chromatography method with post-column derivatization for the detection of aflatoxins in cereals and grains.

A novel, reliable and rapid high-performance liquid chromatography (HPLC) method with post-column derivatization was developed and validated. The HPLC method was used for the simultaneous determination of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) in various cereals and grains. Samples were extracted with 80:20 (v/v) methanol:water and purified using C18 (40-63 µm) solid-phase extraction cartridges. AFs were separated using a LiChroCART-RP-18 (5 µm, 250 × 4.0 mm(2)) column. The mobile phase consisted of methanol:acetonitrile:buffer (17.5:17.5:65 v/v) (pH 7.4) delivered at the flow rate of 1.0 mL min(-1) The fluorescence of each AF was detected at λex = 365 nm and λem = 435 nm. All four AFs were properly resolved within the total run time of 20 min. The established method was extensively validated as a final verification of the method development by the evaluation of selectivity (AFB1, AFB2, AFG1 and AFG2), linearity (R(2) ≥ 0.9994), precision (average SD ≤ 2.79), accuracy (relative mean error ≤ -5.51), robustness (p < 0.0080), ruggedness (p < 0.0100) and average recoveries (89.2-97.8%). The limits of quantification of AFB1, AFB2, AFG1 and AFG2 were 0.080, 0.073, 0.062 and 0.066 ng g(-1), respectively. Finally, the developed method was applied for the analysis of AFs in 45 samples comprising rice (n = 20), wheat (n = 15) and maize (n = 10). The results showed that 65% of rice, 20% of wheat and 80% of maize samples were found contaminated with AFs. Thus, according to the achieved results, it is suggested that the newly developed HPLC method could be effectively applied for the routine analysis of the AFs in different cereals and grains.

Continuation rates and reasons for discontinuation of intra-uterine device in three provinces of Pakistan: results of a 24-month prospective client follow-up.

BACKGROUND: Long-acting reversible contraceptives, such as the intrauterine device (IUD), remain underutilised in Pakistan with high discontinuation rates. Based on a 24-month prospective client follow-up (nested within a larger quasi-experimental study), this paper presents the comparison of two intervention models, one using private mid-level providers branded as "Suraj" and the other using community midwives (CMWs) of Maternal Newborn and Child Health Programme, for method continuation among IUD users. Moreover, determinants of IUD continuation and the reasons for discontinuation, and switching behaviour were studied within each arm. METHODS: A total of 1,163 IUD users, 824 from Suraj and 339 from the CMW model, were enrolled in this 24-month prospective client follow-up. Participants were followed-up by female community mobilisers physically every second month to ascertain continued IUD usage and to collect information on associated factors, switching behaviour, reasons for discontinuation, and pregnancy occurrence. The probabilities of IUD continuation and the risk factors for discontinuation were estimated by life table analysis and Cox proportional-hazard techniques, respectively. RESULTS: The cumulative probabilities of IUD continuation at 24 months in Suraj and CMW models were 82% and 80%, respectively. The difference between the two intervention areas was not significant. The probability distributions of IUD continuation were also similar in both interventions (Log rank test: χ(2) = 0.06, df = 1, P = 0.81; Breslow test: χ(2) = 0.6, df = 1, P = 0.44). Health concerns (Suraj = 57.1%, CMW = 38.7%) and pregnancy desire (Suraj = 29.3%, CMW = 40.3%) were reported as the most prominent reasons for IUD discontinuation in both intervention arms. IUD discontinuation was significantly associated with place of residence in Suraj and with age (15-25 years) in the CMW model. CONCLUSION: CMWs and private providers are equally capable of providing quality IUD services and ensuring higher method continuation. Pakistan's National Maternal Newborn and Child Health programme should consider training CMWs and providing IUDs through them. Moreover, private sector mid-level providers could be engaged in promoting the use of IUDs.

Structural and optical properties of self-assembled chains of plasmonic nanocubes.

Solution-based linear self-assembly of metal nanoparticles offers a powerful strategy for creating plasmonic polymers, which, so far, have been formed from spherical nanoparticles and cylindrical nanorods. Here we report linear solution-based self-assembly of metal nanocubes (NCs), examine the structural characteristics of the NC chains, and demonstrate their advanced optical characteristics. In comparison with chains of nanospheres with similar dimensions, composition, and surface chemistry, predominant face-to-face assembly of large NCs coated with short polymer ligands led to a larger volume of hot spots in the chains, a nearly uniform E-field enhancement in the gaps between colinear NCs, and a new coupling mode for NC chains due to the formation of a Fabry-Perot resonator structure formed by face-to-face bonded NCs. The NC chains exhibited stronger surface-enhanced Raman scattering in comparison with linear assemblies of nanospheres. The experimental results were in agreement with finite difference time domain simulations.

Transthyretin is dysregulated in preeclampsia, and its native form prevents the onset of disease in a preclinical mouse model.

Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinol, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.

Paederia foetida Linn. leaf extract: an antihyperlipidemic, antihyperglycaemic and antioxidant activity.

BACKGROUND: The primary objective of the present investigation is to evaluate the antidiabetic, antihyperlidemic and antioxidant activity of the methanolic extract of the Paederia foetida Linn. (PF) leaf extract in the streptozotocin induced diabetic rats. METHODS: Single intraperitoneal injection (IP) of streptozotocin (60 mg/kg body weight) was used for induction of diabetes is swiss albino (wistar strain) rats. The induction of diabetes was confirmed after 3 days as noticing the increase in blood sugar level of tested rats. PF at a once a daily dose of 100 mg/kg, 250 mg/kg, 500 mg/kg, p.o. along with glibenclamide 10 mg/kg, p.o. was also given for 28 days. On the 28th day rats from all the groups fasted overnight fasted and the blood was collected from the puncturing the retro orbit of the eye under mild anesthetic condition. There collected blood sample was used to determine the antihyperlipidemic, hypoglycemic and antioxidant parameters. RESULTS: The oral acute toxicity studies did not show any toxic effect till the dose at 2000 mg/kg. While oral glucose tolerance test showed better glucose tolerance in tested rats. The statistical data indicated that the different dose of the PF significantly increased the body weight, hexokinase, plasma insulin, high density lipoprotein cholesterol, superoxide dismutase, catalase and glutathione peroxides. It also decreases the level of fasting blood glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, malonaldehyde, glucose-6-phosphate, fructose-1-6-biphosphate and glycated hemoglobin in STZ induced diabetic rats. The histopathology of STZ induce diabetic rats, as expected the test dose of PF extract considerably modulates the pathological condition of various vital organ viz. heart, kidney, liver, pancreas as shown in the histopathology examinations. CONCLUSIONS: Our investigation has clearly indicated that the leaf extract of Paederia foetida Linn. showed remarkable antihyperglycemic activity due to its possible systematic effect involving in the pancreatic and extra pancreatic mechanism. Forever, the antihyperlipidemic activity was exerted possible by lowering the higher level of lipid profile and decreasing the intercalated disc space in the heart. The antioxidant activity of extract was due to inhibition of lipid peroxidation and increasing the SOD, GPx and CAT. It was corroborate that the extract shown the Paederia foetida Linn leaves potential to be act as antidiabetic, antihyperlipidemic and antioxidant properties.

Aflatoxins contamination in Pakistani brown rice: a comparison of TLC, HPLC, LC-MS/MS and ELISA techniques.

Advancement in the field of analytical food-chemistry has explored various experimental techniques for aflatoxins (AFs) quantification. The present study was aimed to compare four different techniques; thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) for the analysis of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) in brown rice (n = 120) being collected from Karachi, Pakistan. All the four assays provide precised, accurate and comparable results. However, some differences were observed. For instance, TLC, HPLC and LC-MS/MS methodologies offered the advantage of the quantification of individual toxins in contrast to ELISA technique. The contamination ranges of AFB1/AFB2 as determined by TLC, HPLC and LC-MS/MS were 1.18-9.97/0.59-1.52, 0.16-10.54/0.26-1.35 and 0.11-10.88/0.38-1.48 µg/kg, respectively. However, AFG1 and AFG2 were not detected in any tested samples. Furthermore, owing to low-detection limit and sensitivity, HPLC and LC-MS/MS methodologies have identified greater number of contaminated samples in comparison to TLC and ELISA techniques. The overall average results of total AFs as provided by HPLC (3.79 µg/kg) and LC-MS/MS (3.89 µg/kg) were found higher in comparison to TLC (3.68 µg/kg) and ELISA (3.70 µg/kg). On the basis of achieved results, it was concluded that TLC, HPLC, LC-MS/MS and ELISA techniques are valuable tool for the quantification of AFs in cereals and grains. Furthermore, HPLC and LC-MS/MS techniques offer an added advantage for the detection of AFs in diminutive levels.

A Prospective Clinical Study of Bacteriological Profile and their Antibiotic Susceptibilty Profile in Patients with Chronic Rhinosinusitis: The Recent Scenario in Northern India.

Objectives: 1. To determine the prevailing scenario of the bacteriological profile of patients with CRS, 2. To identify their antibiotic susceptibility profile. Material and methods: The study was conducted on 100 patients in the Department of ENT and Microbiology from December 2020-2022. Patients above the age of 12 years were evaluated. Those who received antibiotics in the last 12 months. and age < 12 years were excluded. Patients were subjected to a detailed history, clinical and radiological examination. After the informed consent of patients and ethical cleareance, samples were taken from the middle meatus area and studied for antibiotics sensitivity: levofloxacin, vancomycin, amikacin, amoxicillin-clavulanic acid and azithromycin. Results: The study was male predominance (71%), with the maximum of patients in the age group 21-30 years (38%). The most common clinical features were nasal obstruction ( 96%) and mucopurulent discharge (100%). The most common isolate was Staphylococcus aureus (45.16%). In Gram-positive, the maximum resistance was shown to azithromycin and amoxicillin-clavulanic acid and the maximum sensitivity to vancomycin, levofloxacin and amikacin. Conclusions: Antibiotic resistance seems to be emerging for azithromycin and amoxicillin-clavulanic acid at a higher rate. MRSA ( 19.35%) maintains a significant presence with associated increased levels of antibiotic resistance.