Polyphenols and their nanoformulations as potential antibiofilm agents against multidrug-resistant pathogens.

The emergence of multidrug-resistant (MDR) pathogens is a major problem in the therapeutic management of infectious diseases. Among the bacterial resistance mechanisms is the development of an enveloped protein and polysaccharide-hydrated matrix called a biofilm. Polyphenolics have demonstrated beneficial antibacterial effects. Phenolic compounds mediate their antibiofilm effects via disruption of the bacterial membrane, deprivation of substrate, protein binding, binding to adhesion complex, viral fusion blockage and interactions with eukaryotic DNA. However, these compounds have limitations of chemical instability, low bioavailability, poor water solubility and short half-lives. Nanoformulations offer a promising solution to overcome these challenges by enhancing their antibacterial potential. This review summarizes the antibiofilm role of polyphenolics, their underlying mechanisms and their potential role as resistance-modifying agents.

Bacteria can become more difficult to kill by forming a protective layer called a biofilm. This is a problem because infections caused by these bacteria can be difficult to treat. Polyphenols are a natural compound found in plants. They have shown promise in fighting resistant bacteria by stopping bacteria from forming a biofilm. However, polyphenols have some limitations. These limitations can be overcome by using nanomaterials, which are types of tiny particles. When polyphenols are combined with nanomaterials, they become much better at fighting bacteria. This is a promising solution to treating resistant infections caused by biofilm-forming bacteria.

Metal complex as p-type dopant-based organic spiro-OMeTAD hole-transporting material for free-Li-TFSI perovskite solar cells.

Lithium bis(fluorosulfonyl)imide (Li-TFSI) is an efficient p-dopant that has been used to enhance the conductivity of perovskite solar cells (PSCs). However, the performance of the corresponding devices is still not satisfactory due to the impact of Li-TFSI on the fill factor and the short-circuit current density of these PSCs. Herein, a new Mn complex [(Mn(Me-tpen)(ClO4)2-)]2+ was introduced as a p-type dopant into spiro-OMeTAD and was successfully applied as a hole transport material (HTM) for PSCs. Analytical studies used for device characterization included scanning electron microscopy, UV-Vis spectroscopy, current-voltage (IV) characteristics, incident photon to current efficiency, power conversion efficiency (PCE), and electrochemical impedance spectroscopy. The UV-Vis spectra displayed oxidation in the HTM by the addition of a dopant. Moreover, the movement of electrons from the higher orbital of the spiro-OMeTAD to the dopant stimulates the generation of the hole carriers in the HTM, enhancing its conductivity with outstanding long-term stability under mild conditions in a humid (RH ∼ 30%) environment. The incorporation of the Mn complex into the composite improved the material's properties and the stability of the fabricated devices. The Mn complex as a p-type dopant for spiro-OMeTAD exhibits a perceptible PCE of 16.39% with an enhanced conductivity of 98.13%. This finding may pave a rational way for developing efficient and stable PSCs in real environments.

Application of capillary electrophoresis with capacitively contactless conductivity detection for biomedical analysis.

The coupling of capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C4 D) has become convenient analytical method for determination of small molecules that do not possess chromogenic or fluorogenic group. The implementations of CE with C4 D in the determination of inorganic and organic ions and amino acids in biomedical field are demonstrated. Attention on background electrolyte composition, sample treatment procedures, and the utilize of multi-detection systems are described. A number of tables summarizing highly developed CE-C4 D methods and the figures of merit attained are involved. Lastly, concluding remarks and perspectives are argued.

Antibiotics resistance as a major public health concern: A pharmaco-epidemiological study to evaluate prevalence and antibiotics susceptibility-resistance pattern of bacterial isolates from multiple teaching hospitals.

BACKGROUND: Multi Drugs Resistance (MDR) is among the most worrisome healthcare issues resulting from inappropriate and indiscriminate utilization of antimicrobial agents which has compromised the efficacy and reliability of antimicrobial agents (AMAs). This has not only put a huge burden on the health care system but also is a major cause of morbidity and mortality. This project was designed to evaluate the prevalence of various microbial strains among patients admitted to various teaching hospitals and to assess their susceptibility and resistance towards clinically approved antibiotics. METHODS: The study was conducted during August 2021-February 2022 to determine the prevalence of common resistant strains of bacteria and to analyze their susceptibility pattern to the commonly prescribed antibiotics using standard procedures. One hundred and thirty biological samples including urine, blood, cerebrospinal fluid (CSF), wound swabs, pus and sputum were collected from the site of infection from the patients admitted at different wards of North West General Hospital (NWGH), Peshawar, Pakistan, Khyber Teaching Hospital (KTH), Peshawar Pakistan, and Hayat Abad Medical Complex (HMC) Peshawar Pakistan. Samples were collected and cultured following standard hospital procedures. The cultured samples were subjected to identification procedures including Gram staining, morphological characterization of bacterial colonies and biochemical assessments. The identified bacteria were tested for their susceptibility using Kirby-Bauer disc diffusion method. The diameter of Inhibitory Zones (DIZ) was analyzed following Clinical and Laboratory Standards Institute (CLSI) criteria. Minimum Inhibitory Concentrations (MICs) were evaluated using agar dilution method. Antimicrobials sensitivity were presented as antibiogram following CLSI M39 standard. RESULTS: A total of one hundred and thirty biological samples were collected, out of which one hundred and nine samples were positive for bacterial growth and were further processed for detailed analysis. The frequency and type of bacteria isolated from various cultures indicated that Gram negative bacteria (n = 92/109) were more dominant than Gram-positive (n = 17/109) pathogens. The most prevalent bacteria isolated was Escherichia coli (29.35 %), followed by Staphylococcus aureus (15.59 %), and Klebsiella spp, (12.84 %). In addition, other pathogens including, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. showed a prevalence of 9.175 %, 8.25 %, and 5.50 % respectively. As indicated in the antbiogram, several organisms exhibited considerble decline in the sensitivies towards various antibiotics. A high percentage of resistance was observed against some antibiotics including trimethoprim, co-trimoxazole, amoxicillin/clavulanate, ciprofloxacin, piperacillin/tazobactam, cefotaxime and ceftazidime. CONCLUSION: The prevalence of resistant strains of pathogens is increasing day by day, while the antibiotics commonly prescribed against them are losing their efficacy, which is pushing the world to the era of pre-antibiotics. Unfortunately, the discovery of novel antibiotics is limited and researchers speculate that the is pushing towards pre-antibiotics era. Subsequently, efforts must be directed towards ensuring rational antibiotics use to prevent emergence of MDR pathogens. Our findings indicated that Gram negative bacteria including Escherichia coli was most prevalent. Other bacterial strains including S. aureus, Klebsiella spp, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. were found among the causative agents. Unfortunately, considerable decline in the sensitivities of various bacterial isolated were observed towards the tested antibiotics. Previous studies reported the high prevalence of E. coli and S. aureus in clinical samples of Pakistani hospitals including hospitals in Peshawar and thus our findings are in agreement with the previous reports. Pharmacists being experts can play their role by promoting the optimal use of antimicrobial agents and educating healthcare professionals, patients and the public.

Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives.

Leishmaniasis is a vector-borne infection caused by protozoan parasites from the genus leishmania and is among the most neglected tropical diseases. It is highly prevalent disease, affecting about 350 million population worldwide. Only limited number of anti-leishmanial agents are approved for clinical use till now and they are associated with side effects and have limited efficacy. Subsequently, natural products based discovery of more safe and effective drugs against leishmania is under scientific consideration. Various studies reported the efficacy of natural products against intracellular and extracellular forms of leishmania species. This work is aimed to evaluate current literature focused on the anti-leihmanial efficacy of steroidal moieties from natural products and their mechanism of action. Compounds including steroidal saponins, steroidal alkaloids and phytosterols were found to exhibit considerable anti-leishmanial efficacy. For instance, steroidal saponin, (25R)-spirost-5-en-3b-ol,3-O-α-rhamnopyranosyl-(1 â†’ 4)-α-rhamnopyranosyl-(1 â†’ 4)-[a-rhamnopyranosyl-(1 â†’ 2)]-glucopyranoside isolated from A. paradoxum has completely eradicated Leishmania major promastigotes at 50 µg mL-1 dose. Spirostanic saponins isolated from Solanum paniculatum L. were effective against Leishmania amazonensis promastigotes. Turgidosterones isolated from Panicum turgidum exhibited high leishmanicidal potentials against Leishmania donovani promastigotes with IC50 of 4.95-8.03 µg mL-1 and even better activity against amastigotes exhibiting an IC50 of 4.50-9.29 µg mL-1. Likewise, racemoside-A from Asparagus racemosus was found effective against an antimonial sensitive (AG83) and antimonial resistant (GE1F8R) strains of the L. donovani. Moreover, steroidal alkaloids including hookerianamide-1, hookerianamide-H, hookerianamide-J, hookerianamide-K, dehydrosarsalignone, vagenine-A, sarcovagine-C, holaphylline, saracodine, holamine, 15-α hydroxyholamine, holacurtin, N-desmethyl holacurtine and elasticine has exhibited time and dose-dependent efficacy against various strains of leishmania. ß-sitosterol was found active against multiple strains of leishmania. These compounds mainly exhibit their therapeutic efficacy via liberation of ROS, mitochondrial depolarization, morphological and ultra-structural changes, accumulation of lipid droplets, depletion of non-protein thiols and triggering apoptotic pathways. In conclusion, leishmaniasis is a major health problem in many countries. Plants-derived steroids moieties have reveled efficacy against leishmaniasis and is a source of lead compounds. Further detailed molecular studies are warranted for the discovery of more effective and safe anti-leishmanial drugs.

Alzheimer's Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms.

Saponins are triterpenoid or steroidal glycosides and are an important group of naturally occurring compounds of plant origin. They exhibit diverse pharmacological potentials including radical scavenging, as well as neuroprotective, anti-diabetic and anti-inflammatory activities, owing to their diverse chemical scaffolds. Saponins consist of an aglycone part (non-sugar) and a glycone part (sugar) and have at least one glycosidic (C-O sugar bond) linkage present between the glycone and aglycone mostly at C-3. On the basis of the aglycone part, saponins are classified into triterpenoid glycosides, steroid glycosides and alkaloid glycosides. Saponins exhibit neuroprotective activities against various disorders of the central nervous system (CNS) including stroke, Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). They mediate their therapeutic effects by modulation of various pathological targets. This study highlights various neuroprotective mechanisms of saponins including free radical scavenging, modulation of neuroprotective signaling pathways, activation of neurotrophic factors, modulation of neurotransmitters, inhibition of BACE1 enzyme and tau hyper-phosphorylation. The study concludes that saponins have considerable efficacy against various pathological targets of neurological disorders, especially AD, and might be an important source of leads against neurodegenerative disorders.

Antioxidant, Enzyme Inhibitory, and Molecular Docking Approaches to the Antidiabetic Potentials of Bioactive Compounds from Persicaria hydropiper L.

Introduction: Natural products are among the most useful sources for the discovery of new drugs against various diseases. Keeping in view the ethnobotanical relevance ethnopharmacological significance of Polygonaceae family in diabetes, the current study was designed to isolate pure compounds from Persicaria hydropiper L. leaves and evaluate their in vitro and in silico antidiabetic potentials. Methods: Six compounds were isolated from the chloroform-ethyl acetate fractions using gravity column chromatography and were subjected to structure elucidation process. Structures were confirmed using 1H-NMR, 13C-NMR, and mass spectrometry techniques. Isolated phytochemicals were subjected to in vitro antidiabetic studies, including α-glucosidase, α-amylase inhibition, and DPPH, and ABTS antioxidant studies. Furthermore, the in silico binding mode of these compounds in the target enzymes was elucidated via MOE-Dock software. Results: The isolated compounds revealed concentration-dependent inhibitions against α-glucosidase enzyme. Ph-1 and Ph-2 were most potent with 81.84 and 78.79% enzyme inhibitions at 1000 µg·mL-1, respectively. Ph-1 and Ph-2 exhibited IC50s of 85 and 170 µg·mL-1 correspondingly. Likewise, test compounds showed considerable α-amylase inhibitions with Ph-1 and Ph-2 being the most potent. Tested compounds exhibited considerable antioxidant potentials in both DPPH and ABTS assays. Molecular simulation studies also revealed top-ranked confirmations for the majority of the compounds in the target enzymes. Highest observed potent compound was Ph-1 with docking score of -12.4286 and formed eight hydrogen bonds and three H-pi linkages with the Asp 68, Phe 157, Phe 177, Asn 241, Glu 276, His 279, Phe 300, Glu 304, Ser 308, Pro 309, Phe 310, Asp 349, and Arg 439 residues of α-glucosidase binding packets. Asp 68, Glu 276, Asp 349, and Arg 439 formed polar bonds with the 3-ethyl-2-methylpentane moiety of the ligand. Conclusions: The isolated compounds exhibited considerable antioxidant and inhibitory potentials against vital enzymes implicated in T2DM. The docking scores of the compounds revealed that they exhibit affinity for binding with target ligands. The enzyme inhibition and antioxidant potential of the compounds might contribute to the hypoglycemic effects of the plant and need further studies.

Photocatalytic remediation of methylene blue using hydrothermally synthesized H-Titania and Na-Titania nanotubes.

Although nanotube is among the most effective morphology of Titania due to its unilateral pathway for photo-generated charge transfer and mechanical stability, its performance is still hampered by high recombination. In the present study, to further improve the photocatalytic degradation performance of Titania, univalent elements of H and Na were respectively ion-exchanged into the Titania nanotubes (TNTs). The photocatalyst was characterized using XRD, TEM, ICP-AES, and FTIR. The modified samples displayed enhanced photocatalytic degradation performance over Degussa TiO2 under UV-A light illumination of MB. The rate constants of NaTNT and HTNT were 16 and 13 times that of Degussa TiO2. Specifically, the Na-TNTs showed better photocatalytic degradation activity than H-TNTs with a rate constant of 0.12 min-1 while the latter showed 0.09 min-1. The optimum adsorption and photocatalytic performance of NaTNT were determined at pH 6 achieving about 99% MB removal within 10 min of irradiation. The ion exchange NaTNT displayed excellent reusability after the fifth cycle of the photocatalytic tests and superoxide radicals were experimentally determined to be the main reactive oxygen species involved in the photocatalytic degradation of MB.

An Epidemiological Study of COVID-19 Cases in Al-Leith, Saudi Arabia.

Background and objective Ever since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in December 2019, more than 0.550 million cases of coronavirus disease 2019 (COVID-19) have been reported in the kingdom of Saudi Arabia (KSA) and the number is on the rise. In this study, we aimed to perform an epidemiological analysis of COVID-19 cases in Al-Leith, KSA. Methods A community-based descriptive study was carried out to assess the epidemiology of COVID-19 in Al-Leith, KSA. The relevant data were collected using a questionnaire designed for this study, which included questions on basic information and characteristics in addition to data on COVID-19. Data were analyzed using the SPSS Statistics software (IBM, Armonk, NY). Results The significant findings were as follows: people aged between 26-40 years were more affected (55.7%) than other age groups, and more than half (74.1%) of COVID-19 patients were female; most of them were employed (85, 48,9%), and most of those got infected through direct contact (137, 78.7%) with other infected people. About 163 (93.7%) cases were asymptomatic, and 168 (96.6%) cases were notified to the health authorities. The findings also illustrated that 78 (44.8%) COVID-19 cases suffered from psychological impact due to infection; 83 (47.7%) cases had at least one case in the family before they became infected. The majority of cases (93.7%) suffered from symptomatic COVID-19. A considerable number of COVID-19 patients did not follow precautions before and after infection. Conclusions The study concluded that various age groups were susceptible to developing COVID-19, and direct contact was the main mode of transmission. Moreover, a considerable number of infected people did not adhere to precautionary measures.

An organic hole-transporting material spiro-OMeTAD doped with a Mn complex for efficient perovskite solar cells with high conversion efficiency.

2,{2}',7,{7}'-Tetrakis(N,N-di-p-methoxyphenylamine)-9,{9}'-spiro-bi-fluorene(spiro-OMeTAD) has often been used as a hole-transporting material (HTM) in mesoscopic perovskite solar cells (PSCs). However, its potential applications are limited due to its poor conductivity of approximately 10-6 to 10-5 cm2 V s-1 in pristine form, and this influences the stability and intrinsic hole conductivity of the device. In this work, a Mn complex [(Mn(Me-tpen)(ClO4)2 -)]2+ is introduced as a p-dopant to improve the properties of spiro-OMeTAD-based PSCs, including the optical, electrical, conductivity, and stability properties. Interestingly, the use of spiro-OMeTAD with an optimum concentration (1.0% w/w) of Mn complex in mesoscopic PSCs achieves a remarkable power conversion efficiency of 17.62% with a high conductivity of 99.05%. Spiro-OMeTAD with Mn complex as a p-dopant under UV-vis spectroscopy shows a different peak at 520 nm, confirming that oxidation occurs upon the addition of the Mn complex. The enhanced efficiency of the PSCs may be attributed to an increase in the optical and electrical properties of the HTM in the spiro-OMeTAD doped Mn complex.