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Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1–5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8–5.3 μg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to β-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus

The interaction of the important plasma protein, human serum albumin (HSA), with two monoterpenes found in cumin oil, i.e., cuminaldehyde (4-isopropylbenzaldehyde) and cuminol (4-isopropylbenzyl alcohol), was studied in this paper. Both experimental and computational methods were utilized to understand the mechanism of binding. The UV absorption profile of HSA changes in the presence of both cuminaldehyde and cuminol, due to the interaction between HSA with both monoterpenes. The intrinsic fluorescence intensity of HSA was also quenched on the sequential addition of both ligands, due to change in the microenvironment of the fluorophore present in the former. Quenching of HSA by cuminaldehyde was much higher in comparison to that in the presence of cuminol. Fluorescence quenching data were analyzed using modified Stern-Volmer and Lineweaver-Burk methods, which suggested that the binding mechanism was of a static type for both ligands. In both cases, the binding was favored by the domination of hydrophobic as well as hydrogen bonding/Van der Waals forces. Both ligands partially unfolded the secondary structure of HSA, although the effect of cuminaldehyde was more pronounced, as compared to cuminol. The preferred binding site of cuminaldehyde and cuminol inside HSA was also the same; namely, drug binding site 1, located in subdomain IIA. The study showed that cuminaldehyde binds strongly with albumin as compared to its alcohol counterpart, which is due to the more hydrophobic nature of the former.

The objective of this analysis is to establish the potential of biodegradable agro-industrial waste materials as biosorbents in the solid-phase extraction (SPE) technique for sample preparation. In this regard, waste coffee husk (CH) powder was collected, washed, treated chemically, characterized, and applied as an SPE adsorbent to extract pantoprazole from the wastewater samples. Sample detection was accomplished using the UPLC-MS/MS system. The positive mode of electrospray ionization was exploited for the ionization of the sample, and quantification of the target analyte was performed by the multiple reaction monitoring modes. The precursor to product ion transition of 384.02→1380.05 and 384.02→200.05 was used as qualifiers and quantifiers, respectively. Optimization of the particle size, adsorbent dose, and contact time were evaluated to select the best combination of features. The efficiency and regeneration capability of the CH were compared with respect to a commercially available silica-based C18 SPE adsorbent, and it was found that CH possessed comparable (~50%) extraction, as well as regeneration capacity (~95%). The developed biosorbent was applied in a wastewater sample spiked with the target analyte and recovery studies were performed, which found a range of 93.0 to 102.0% with a %RSD of 3.72 to 12.7%. Thus, CH can be exploited as a ‘greener’ replacement for the commercially available adsorbents for the extraction/retention of active pharmaceutical ingredients present in water/wastewater samples.

The technological progression is raised as a hybrid ecosystem with the industrial Internet of Things (IIoT). Among them, healthcare is also broadly unified with the Internet of Things to develop an industrial forthcoming system. Utilizing this type of system can be facilitating optimum patient monitoring, competent diagnosis, intensive care, and including the appropriate operation against the existing critical diseases. Due to enormous data theft or privacy leakage, security, and privacy towards patient-based informative data, the preservation of personal patients’ informative data has now become a necessity in the digitized community. The produced article is underlined on handsomely monitoring, perceptively extracted keyframe, and further processed lightweight cosine functions using hybrid way chaotic map keyframe image encryption. Initially, a regular concept of extracted keyframe is deployed to salvage meaningful detected frames by transmitting an alert autonomously to the administration. Then, lightweight cosine function for encryption is employed. This encryption incorporates keyframe exceedingly secure and safe from the outside world or any adversary. Our proposed methodology validates effectiveness throughout the IIoT ecosystem. The produced outcome is highly acceptable and has minimum execution time, robustness, and reasonably adopted cost-effective, secure parameter than any other (keyframes) image encryption methods. Furthermore, this methodology has optimally reduced bandwidth, essential communicating price, transmission cost, storage, and immediately judicious analysis of each occurred activity from the outside world or any adversary to remain secure and confident about the real patient-based data in the smartly developed environment.

In recent times, nanoparticles (NPs) have found increasing interest owing to their size, large surface areas, distinctive structures, and unique properties, making them suitable for various industrial and biomedical applications. Biogenic synthesis of NPs using microbes is a recent trend and a greener approach than physical and chemical methods of synthesis, which demand higher costs, greater energy consumption, and complex reaction conditions and ensue hazardous environmental impact. Several microorganisms are known to trap metalsin situand convert them into elemental NPs forms. They are found to accumulate inside and outside of the cell as well as in the periplasmic space. Despite the toxicity of NPs, the driving factor for the production of NPs inside microorganisms remains unelucidated. Several reports suggest that nanotization is a way of stress response and biodefense mechanism for the microbe, which involves metal excretion/accumulation across membranes, enzymatic action, efflux pump systems, binding at peptides, and precipitation. Moreover, genes also play an important role for microbial nanoparticle biosynthesis. The resistance of microbial cells to metal ions during inward and outward transportation leads to precipitation. Accordingly, it becomes pertinent to understand the interaction of the metal ions with proteins, DNA, organelles, membranes, and their subsequent cellular uptake. The elucidation of the mechanism also allows us to control the shape, size, and monodispersity of the NPs to develop large-scale production according to the required application. This article reviews different means in microbial synthesis of NPs focusing on understanding the cellular, biochemical, and molecular mechanisms of nanotization of metals.

Parthenolide, a strong cytotoxic compound found in different parts of Tarchonanthus camphoratus which motivated the authors to develop an optimized microwave-assisted extraction (MEA) method using Box–Behnken design (BBD) for efficient extraction of parthenolide from the stem of T. camphoratus and its validation by high-performance thin-layer chromatography (HPTLC) and cytotoxic analysis. The optimized parameters for microwave extraction were determined as: 51.5 °C extraction temperature, 50.8 min extraction time, and 211 W microwave power. A quadratic polynomial model was found the most suitable model with R2 of 0.9989 and coefficient of variation (CV) of 0.2898%. The high values of adjusted R2 (0.9974), predicted R2 (0.9945), and signal-to-noise ratio (74.23) indicated a good correlation and adequate signal, respectively. HPTLC analyzed the parthenolide (Rf = 0.16) content in T. camphoratus methanol extract (TCME) at λmax = 575 nm and found it as 0.9273% ± 0.0487% w/w, which was a higher than expected yield (0.9157% w/w). The TCME exhibited good cytotoxicity against HepG2 and MCF-7 cell lines (IC50 = 30.87 and 35.41 µg/mL, respectively), which further supported our findings of high parthenolide content in TCME. This optimized MAE method can be further applied to efficiently extract parthenolide from marketed herbal supplements containing different Tarconanthus species.

Bergenin and menisdaurin are biologically active components which are found in plant Flueggea virosa (Phyllanthaceae). Bergenin has pharmacological actions such as chemopreventive and antihepatotoxic while menisdaurin has an anti-viral activity which needs its evaluation by an analytical method (UPLC-PDA method) that can be applied to the quality control of pharmaceutical preparations. The developed UPLC-PDA method was applied for identification and quantification of standards bergenin and menisdaurin in the methanol extract of F. virosa (FVME). The analysis was carried out using Eclipse C18 (4.6 × 100 mm, 3.5 µm) UPLC column. The optimized chromatographic condition was achieved at 0.16 mL/min flow rate using gradient system with acetonitrile and water as mobile phase. Both biomarkers were measured at λmax 235 nm in PDA detector at ambient temperature. The developed method furnished sharp and intense peaks of menisdaurin and bergenin at Rt = 2.723 and 3.068 min, respectively along with r2 > 0.99 for both. The recoveries of bergenin and menisdaurin were found in the range of 99.37–101.49% and 98.20–100.08%, respectively. With other validation data, including precision, specificity, accuracy, and robustness, this method demonstrated excellent reliability and sensitivity. The separation parameters i.e. retention, separation, and resolution factors for resolved standards (bergenin and menisdaurin) were >1, which showed good separation. The quantity of bergenin and menisdaurin in the FVME sample was found as 15.16 and 3.28% w/w, respectively. The developed UPLC-PDA method could be conveniently adopted for the routine quality control analysis.

Solanaceae is one of the highly diverse plant families of which Solanum is the largest genera (1700 species) containing several pharmacological properties like anticancer and antimicrobial. This motivated us to explore the anticancer (against HepG2, HEK-293, and MCF-7 cells) and antimicrobial (against S. aureus, E. coli, P. aeruginosa, and C. albicans) properties of S. schimperianum, S. villosum, S. coagulans, S. glabratum, S. incanum, and S. nigrum along with rutin estimation by UPLC-PDA method. Of the studied Solanum extracts, S. nigrum exhibited significant cytotoxic property against HepG2 (IC50: 20.4 μg/mL) and MCF-7 (IC50: 30.1 μg/mL); S. coagulans showed toxicity against HepG2 (IC50: 28.4 μg/mL) and HEK-293 cells (IC50: 25.7 μg/mL) compared to 5-Fluorouracil (standard). Compared to these, extracts of S. coagulans and S. glabratum exhibited relatively high antimicrobial potency (MIC: 0.4-1.6 mg/mL). Nonetheless, all Solanum extracts significantly reduced the biofilm against PAO1-strain. Rutin was detected in all extracts with the highest content (53.79 μg/mg) in S. coagulans that supported its strong antimicrobial and anticancer properties. Molecular docking analysis showing strong binding of rutin with human DNA and proteins (DNA Topoisomerase IIα and E. coli DNA gyrase B) supported the anticancer and antimicrobial activities of Solanum species.

The effects of 50% Drink of Myrica rubra (MRD) on the cardiovascular system of the rat and on the platelets aggregation of rats and guinea pigs were studied. Different groups of male Wistar rats were treated either with 50% Myrica rubra drink as drinking vehicle (4 weeks) or water. The animals were then prepared for the measurement of arterial blood pressure and heart rate, ECG, sensitivity of the baroreceptors, platelets’ aggregation, blood clotting time and cardiac parasympathetic ganglia. The mechanism of action of any induced effect was elucidated using different receptor blockers. Treatment induced a significant decrease in the arterial blood pressure and heart rate on Wistar rats, but no significant changes in the ECG were observed. Pretreatment of rats with MRD 10 or 20 ml/kg (i. p.) significantly suppressed vagal electrical stimulation to the heart and nicotine-induced bradycardia, via decreasing phenylephrine-induced rise in the arterial blood pressure and the reflexly-induced bradycardia. It significantly suppressed the Baroreceptor Sensitivity Index (BSI). The treatment also significantly suppressed ADP-induced platelets aggregation in rats and arachidonic acid-induced aggregation in guinea pigs. All these actions seemed to be mediated by the MRD constituents such as proanthocyanidins, polyphenols and flavonoids. The decreases in the heart rate and BSI were probably caused by an inherent ability to block the parasympathetic ganglia. The results of this study regarding the effects of MRD actions on the cardiovascular system and platelets qualify the drink to be classified as a functional food.

Chinese arbutus (Myrica rubra) fruits or Yumberry, are stony red fruits with berry-like edible portions growing in China, India, Japan and some other south eastern Asian countries. A 50% juice under the trade name Yumberry is available in some countries. It is rich in polyphenols and proanthocyanidins. This study investigated the effect of 4 weeks administration of the juice as a substitute for the normal rats' drinking water on ethanol- and stress-indomethacin-induced ulcer, carrageenan-induced paw inflammation and croton oil-induced hemorrhoids in male Wistar rats. Consumption of Yumberry drink for 4 weeks almost completely protected the rats against the alcohol-induced gastric ulcers (p < 0.05) with no significant effect against the combined cold stress-indomethacin-induced ulcers (p < 0.05). The treatment significantly suppressed carrageenan-induced oedema in the rat's paw in a time-dependent manner (p < 0.05 to p < 0.001, N = 8). The treatment also significantly suppressed experimentally-induced hemorrhoids by 74 ± 5.9% (p < 0.001, N = 8). The different mechanisms of actions of the observed beneficial actions are discussed. The results of this study pointed for the first time the direct protective effects of M. rubra beverage on the gastric mucosa and its direct anti-inflammatory effect against skin and rectal inflammations. Key words: Bayberry, gastric ulcers, inflammation, hemorrhoids.

We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy.

Fenugreek (Trigonella foenum-graceum) is an herbal medicine widely used in the traditional medicine to alleviate many diseases including diabetes. Many studies proved its efficacy in reducing blood sugar in diabetic patients. Concurrent administration of fenugreek and glibenclamide may affect bioavailability of glibenclamide. For this reason this study was designed to clarify effect of fenugreek ingestion on bioavailability of glibenclamide in beagle dogs. 4 beagle dogs were administered either glibenclamide alone or glibenclamide with fenugreek and bioavailability of glibenclamide in each of these groups was estimated utilizing HPLC-fluorescence detector method. The method was validated and the results were compared by paired t-test. The method of analysis was linear in the range from 5 to 400 ng/ml and possessed highly specificity and high intra and inter-day precision {1.80 to 9.16% and 5.82 to 10.40% respectively as C.V(%)}. Recovery of glibenclamide (relative to warfarin as IS) was 98.7 to 105.1%. Fenugreek ingestion increased bioavailability of glibenclamide significantly (p< 0.05) compared to control group. The exact mechanism of increased bioavailability of glibenclamide was not studied although literature review of fenugreek constituents points to possibility of increased absorption and/or displacement of glibenclamide from protein binding sites. Key words: Fenugreek, glibenclamide, Beagle dogs, HPLC, bioavailability.

Biomarker β-amyrin was analyzed in the leaves of four different Acacia species (A. salicina, A. loreta, A. hamulosa and A. tortilis) grown in Kingdom of Saudi Arabia by a validated HPTLC method. The chromatography was performed on glass-backed silica gel 60 F254 HPTLC plates using solvents toluene: methanol (9:1, v/v) as mobile phase. The developed TLC plate was derivatized with anisaldehyde and scanned at 520 nm. A sharp peak of β-amyrin was found at Rf=0.58±0.01. The r2 and the linear regression equation for β-amyrin was found to be 0.991 and 19.913X+107.803, respectively in the concentration range of 100-800 ng. The percentage of β-amyrin was found to be maximum 2.70% w/w in A. tortilis, 1.85% w/w in A. loreta and 1.80% w/w in A. hamulosa while it was totally absent in A. salicina. This study conceives maiden reporting of quantification of β-amyrin in four different species of Acacia by validated HPTLC method. The developed method for the analysis of β-amyrin was proved to be reproducible by statistical analysis hence it can be employed for further analysis of β-amyrin in plasma, other biological fluids and in finished products available in the market.

A new bioactive oxygenated homoditerpenic compound along with one known compound from the antimicrobial active ethanol extract of leaves of an endemic plant Centaurothamnus maximus was isolated. The n -hexane, dichloromethane, ethyl acetate and ethanol fractions of C. maximus leaves were evaluated for their antimicrobial potential by using standard agar well diffusion method against various microorganisms viz. B. subtilis, S. aureus, E. coli, P. aeruginosa, C. albicans and M. smegmatis. The results revealed that only ethanol extract was active against all microbes except the fungus C. albicans. A new compound 2α, 3α-dihydroxy-8α-methoxy-15-hydroxy-methylene- pimar-5,9 (11)-diene (CM-1) was isolated along with a known compound α-D-xylose (CM-2) from ethanol extract by reverse phase (RP-18) column chromatography and 1D and 2D NMR (DEPT, COSY, HMBC and HSQC) aided by EIMS mass and IR spectra were used to establish the structure. CM-1 was found to be active against B. subtilis, S. aureus and M. smegmatis (P0.005) at MIC 20 μg/ml. Findings of this study may provide a lead for synthesis of more potent antimicrobial agents to serve the humanity against multidrug-resistant bacterial infections.

Background: This study dealt with the effect of the subchronic toxicity of Myrica rubra fruit beverage drink (MRD) in rats and its hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatotoxicity. Methodology: Different groups of normal male and female Wistar rats were treated with 50% MRD as drinking vehicle (13 weeks), as substitution of the normal drinking water. Coulter Counter was used for red blood corpuscles (RBCs) and white blood corpuscles (WBCs) count. The Reflotron instrument and Reflotron haemoglobin kit used for determination of haemoglobin content, while the Reflotron strips for determination of blood glucose, total triglycerides and cholesterol contents, blood enzymatic levels, and bilirubin. Atomic absorption spectroscopy was used for determination of blood Na+, Mg++ and Ca++ concentrations. Principal findings: Treatment induced significant increases in the red blood corpuscles (RBCs) count, haematocrit and haemoglobin content. It also significantly decreased plasma levels of total cholesterol and the low-density lipoproteins (LDL) without affecting the levels of high-density lipoproteins (HDL), glucose, triglycerides and bilirubin, together with the significant decrease in hepatic malonaldehyde production. The treatment resulted in significant reductions in the enzymes alanine transiminase (ALT), aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) and a significant diuretic effect. Conclusion: The results of the study point to the potential of Myrica rubra fruit drink to act as a new functional food.