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Salinization of aquatic ecosystem, abrupt climate change, and anthropogenic activities cause adverse impact on agricultural land/soil as well as the aquaculture industry. This experimental study was designed to evaluate different biomarkers of oxidative stress, antioxidant enzymes, and genotoxic potential of diverse salinities of brackish water on freshwater fish. A total of 84 fresh water mrigal carp (Cirrhinus mrigala) were randomly segregated and maintained in four groups (T0, T1, T2, and T3) in a glass aquarium under similar laboratory conditions at various salinity levels (0, 3, 5, and 7 parts per thousand) to determine the pathological influence of brackish water. All the fish in groups T1, T2, and T3 were exposed to various salinity levels of brackish water for a period of 90 days while the fish of group T0 served as the control group. The experimental fish reared in different groups T1, T2, and T3 displayed various physical and behavioral ailments. The results revealed significantly augmented quantity of different oxidative stress indicators including reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) in different visceral tissues (kidneys, liver, and gills) of exposed fish. Different antioxidant enzymes such as reduced glutathione (GSH), peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) along with total proteins were remarkably reduced in the kidneys, gills, and liver tissues. Results showed significantly increased values of different nuclear abnormalities (erythrocyte with micronucleus, erythrocyte with condensed nucleus, and erythrocyte with lobed nucleus) and morphological changes (pear shaped erythrocyte, spindle-shaped erythrocytes, and spherocyte) in red blood cells of experimental fish. The results on genotoxic effects exhibited significantly increased DNA damage in isolated cells of liver, kidneys, and gills of exposed fish. The findings of our experimental research suggested that brackish water causes adverse toxicological impacts on different visceral tissues of fresh water fish at higher salinity level through disruption and disorder of physiological and biochemical markers.

The innate immune system is the main and first line of defense mechanism present in the human body, which acts against a foreign antigen. To function it utilize several mechanisms, among those are the primary one is recognizing the foreign antigen which is accomplished via decidedly complicated group of molecules termed as pattern recognition receptors (PRRs), which perceive various diverse structures present on the pathogen known as pathogen-associated molecular patterns (PAMPs). PRPs include several classes of receptors’, functions, and nature of these receptors vary from each other depending upon the molecular composition of PAMPs they detect. However, the Toll-like receptors (TLRs) are among the class of PRPs, which are studied widely. In this review, we have presented the contemporary understanding of pathogens recognition by various receptor classes including PRRs. In addition, we also discuss PRPs associated signaling pathways associated with antimicrobial immune response triggering.

Though the incidence of several cancers in Western societies is regulated wisely, some cancers such as breast, lung, and colorectal cancer are currently rising in many low- and middle-income countries due to increased risk factors triggered by societal and development problems. Surgery, chemotherapy, hormone, radiation, and targeted therapies are examples of traditional cancer treatment approaches. However, multiple short- and long-term adverse effects may also significantly affect patient prognosis depending on treatment-associated clinical factors. More and more research has been carried out to find new therapeutic agents in natural products, among which the bioactive compounds derived from plants have been increasingly studied. Naringin and naringenin are abundantly found in citrus fruits, such as oranges and grapefruits. A variety of cell signaling pathways mediates their anti-carcinogenic properties. Naringin and naringenin were also documented to overcome multidrug resistance, one of the major challenges to clinical practice due to multiple defense mechanisms in cancer. The effective parameters underlying the anticancer effects of naringenin and naringin include GSK3β inactivation, suppression of the gene and protein activation of NF-kB and COX-2, JAK2/STAT3 downregulation, downregulation of intracellular adhesion molecules-1, upregulation of Notch1 and tyrocite-specific genes, and activation of p38/MAPK and caspase-3. Thus, this review outlines the potential of naringin and naringenin in managing different types of cancers.

One of the leading causes of death worldwide is cancer. Excessive production of tumor necrosis factor (TNF)-α is known to activate nuclear transcription factor (NF)-κB, which plays a lethal role in the onset of multiple disorders including cancer. In this study, we aimed to determine the therapeutic role of novel gold nanoparticles conjugated with citrate (AuNPs-CIT) on the elevated expression of TNF-α in breast cancer cells. AuNPs-CIT were synthesized by the citrate-reduction method and were characterized by UV-VIS spectroscopic analysis, zeta-potential analysis, and size analysis. The potential of these newly generated AuNPs-CIT particles was tested on phorbol 12-myristate 13-acetate (PMA)-stimulated cancer cells. Our data showed that the AuNPs-CIT were spherical, with a mean size of 21.3±0.65 nm and a stabilized zetapotential at −41.4±0.98 mV. These newly generated AuNPs-CIT nanoparticles inhibited PMA-induced activation and nuclear translocation of NF-κB p65 in MCF-7 cells. They also have the tendency to block TNF-α expression in stimulated cancer cells. In conclusion, AuNPs-CIT inhibits PMA-induced TNF-α mRNA and protein expression via deactivation of NF-κB signaling in breast cancer cells. These findings suggest that AuNPs-CIT might be useful in cancer treatment.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients’ co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

As compared to conventional techniques, currently nanotechnology has gained significant attention of scientists for the development of plant-based natural nanoparticles (NPs) due to their safety, effectiveness, and environment friendly nature. The current study was aimed for development, characterization (energy-dispersive X-ray, ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy), and evaluation of the biological efficiency of black pepper (BP; Piper nigrum) fruit-based gold NPs (BP-AuNPs) through different in vitro and in vivo assays. BP extract revealed maximum antibacterial and antifungal potential against Escherichia coli (24 mm) and Aspergillus flavus (47 mm), respectively. However, BP-AuNPs (200 µg·mL−1) inhibited the urease, xanthine oxidase, and carbonic acid-II activities with a percent inhibition of 83.11%, 91.28%, and 86.87%, respectively. Further, the anti-inflammatory effect of BP extract at the dose of 100 mg·kg−1 was 72.66%, whereas for BP-AuNPs it was noticed to be 91.93% at the dose of 10 mg·kg−1. Similarly, the extract of BP and prepared AuNPs demonstrated significant (p < 0.01) sedative effect at all tested doses. The BP-AuNPs catalytically reduced methyl orange dye. Results suggest that BP-AuNPs possess significant biological activities, and further studies must be conducted to identify the probable mechanism of action associated with these activities.

Urease is a metallo-protein in which two nickel (Ni) atoms are present at the active site. It is found in all the organisms such as, bacteria, fungi, plants, and in algae. Urease enzymes are also involved in catalyzing the hydrolysis of urea into CO2 and NH3. Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. Current research work aimed to purify the three di-naphthodiospyrols namely; 5,4 -dihydroxy-1-methoxy-6,6 -dimethyl7,3-binaphthyl-1,4,5,8-tetraone (1), 5,8 -dihydroxy-5-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4 -tetraone (2) and 8,5,8-trihydroxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (3) from the chloroform fraction of Diospyros lotus roots. The pure constituents (1-3) were evaluated for their urease inhibitory activity. Compounds (1-3) exhibited potent activity with IC50 value of 28.27 ± 1.68, 20.57 ± 2.00, 27.12 ± 2.45 µM respectively, when compared with standard thiourea (IC50 = 21.23 ± 0.12 µM). The pure isolated compounds (1-3) were also subjected to in silico studies to know their binding pattern with enzyme. The binding orientation and interactions with the important residues of urease enzyme revealed that the three compounds inactivate the enzyme activity by interacting with Ni bi-center as well as with the tailpiece residues.

Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects.The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model.Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis.Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Background Ifosfamide (IFS) has potential complications such as nephropathy and hemorrhagic cystitis (HC). Although mesna can prevent IFS-induced cystitis by direct binding and neutralization of acrolein, HC symptoms have still been observed clinically in most of these cases. Celery is a powerful healing vegetable that has antioxidant, anti-inflammatory, and anticancer effects. The current study evaluated the synergistic effects of mesna and celery seed on IFS-induced HC in rabbits. Methods Twenty male rabbits (four groups) were administered distilled water, IFS, mesna, and mesna+celery seed cotherapy (MCC) for three weeks. The serum and urinary bladder of experimental rabbits underwent biochemical (TNF-α, MDA, iNOS, SOD, GPx, and CAT), histopathological and ultrastructural investigations to evaluate the structural changes of the urinary bladder (UB). Results IFS injection resulted in severe cystitis with a remarkable increase in the scale of hematuria, elevations of TNF-α, MDA, and iNOS activity, and reduced activity of SOD, GPx, and CAT antioxidants. Additionally, the structure of UB exhibited evident mucosal edema and ulceration. In contrast, the MCC regimen group revealed partial synergistic improvement of all mentioned parameters. Conclusion IFS induced cystitis by releasing acrolein, which exerted a significant role in the pathogenesis of HC. In contrast, the MCC intake partially ameliorated the UB damage through its antioxidant and anti-inflammatory effects., Graphical Abstract

Herbal plants represent a new source of hypoglycemic antidiabetic drugs; haematological and histopathological studies of methanol extract of Deverra tortuosa in streptozotocin-induced diabetic rats were investigated in vivo. A single intraperitoneal injection of 160 mg/kg bodyweights of streptozotocin was used to cause diabetes. Blood glucose levels were tested with an AccuCheck Advantage II glucometer and blood glucose test strips. After diabetes was confirmed, animals were orally treated with the extract, metformin, and insulin according to the experimental design. After extract therapy, histological alterations in the pancreas of diabetic rats were investigated. When compared to a control group, daily oral administration of D. tortuosa extract (300 mg/kg body weight) plus metformin (100 mg/kg) had a positive effect on blood glucose levels as well as showed an increased number of white blood cells (WBCs) and red blood cells (RBCs). The treatment with the extract for two weeks showed a positive impact on pancreatic histopathological changes in the groups with the diabetic rats. Phenolic fraction of the methanol extract was screened by the liquid chromatography-mass spectroscopy (LC-MS) method, which unveiled the existence of flavonoid compounds and phenolics as kaempferol, rutin, isorhamnetin-3-O-rutinoside, caffeic acid, and 4-hydroxybenzoic acid 4-O-glucoside. The results confirmed the use of the plant as an antidiabetic agent; the research recommended further studies on the plant to use the plant as an antidiabetic drug, where the plant extract also showed improvement in blood parameters.

A novel encapsulated deep eutectic solvent (DES) was introduced for biodiesel production via a two-step process. The DES was encapsulated in medical capsules and were used to reduce the free fatty acid (FFA) content of acidic crude palm oil (ACPO) to the minimum acceptable level (

Pistacia integerrima leaf galls are used in several traditional medicines to cure many diseases such as diarrhea, asthma, fever, cough, vomiting, and hepatitis. The main goal of the present investigation was to assess the antidiarrheal effect of the Pistacia integerrima extracts/fractions and four isolated flavonoid compounds (1-4) on mice. An in vivo assay involving castor-oil-induced diarrhea was used to evaluate the antidiarrheal potential of extracts/fractions at 100, 200, and 400 mg/kg p.o., as well as isolated compounds at 5, 10, and 20 mg/kg p.o. Pretreatment of mice with extracts/fractions significantly attenuated castor-oil-induced diarrhea in a dose-dependent manner. Among all crude extracts and fractions, the ethyl acetate extract was the most effective with 100% protection against diarrhea followed by chloroform (75% protection) at 400 mg/kg p.o. Although all the isolated compounds exhibited strong antidiarrheal activity, isolated compounds 1 and 4 demonstrated 100% protection against diarrhea. Moreover, docking models were performed using the Molecular Operating Environment (MOE) and AutoDock software and suggested that the extracts and isolated compounds exert antidiarrheal activity by inhibiting mu-opioid and delta-opioid receptors. Therefore, our finding affords a strong pharmacological basis for the traditional use of P. integerrima galls in the treatment of diarrhea.

Currently, nanotechnology is gaining massive attention compared to conventional methods as the biosynthesis of plant-based nanoparticles is considered safe, effective, and ecofriendly. Therefore, keeping in view the importance of nanotechnology, the present study was designed to synthesize, characterize, and evaluate the biological effectiveness of saffron stigma-based gold nanoparticles (SS-AuNPs) for theirin vitroandin vivobiological properties. These gold nanoparticles were characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). The highest antibacterial effect was observed by the saffron extract againstEscherichia coli(22 mm). SS-AuNPs significantly inhibited the activity of enzyme urease (54.98%) and CA-II (64.29%). However, the nonsignificant inhibitory effect was observed in the case of α-chymotrypsin. Maximum analgesic (84.98%) and antiinflammatory (88.98%) effects were observed for SS-AuNPs (10 mg/kg). Similarly, SS-AuNPs demonstrated a significant (P< 0.01) sedative effect at all tested doses.

Fernandoa adenophylla (Wall. ex G. Don) Steenis is traditionally used to cure various diseases and can be included as an ingredient in massage oils, which are supposed to comfort muscular tension and pain. This study was designed to assess the antinociceptive, muscle relaxant, and molecular docking properties of a novel compound, namely, (5aR,5a1R,6R,7aS,14bR,15R)15-hydroxy-7a-methyl-6-(2-methylprop-1-en-1-yl)-7,7a,14b,15-tetrahydro-5H-t-5a,15methanobenzo[g]benzo[5,6]azuleno[1,8-bc]chromene-5,9,14,16(5a1H,6H)- tetraone (peshawaraquinone), isolated from the methanolic extract of F. adenophylla in an animal model. The chemical structure of the isolated compound was elucidated using advanced spectroscopic techniques and further confirmed by XRD analysis. Compound 1 was tested against hot plate-induced noxious stimuli at various doses (2.5, 5, 10, and 15 mg/kg i.p.). The muscle relaxation potency of compound 1 was evaluated in the inclined and traction test, while the open-field test was used for the determination of sedative potential. The isolated compound was also subjected to acute toxicity analysis. The compound was then subjected to molecular docking analysis to determine the exact mechanism of action. Compound 1 demonstrated significant (p < 0.05) analgesic effect in a dose-dependent manner. A noticeable muscle relaxant effect was observed with the passage of time in both experimental models. The compound 1 showed a significant (p < 0.05) sedative effect, and in an acute toxicity study, the compound 1 was devoid of any noxious effects. The docking studies showed preferential affinity for μ-opioid and GABAA receptors. Hence, the prospective antinociceptive and muscle relaxant and sedative properties are probably mediated through these two target interactions.

Saffron (Crocus sativus L., family Iridaceae) is used traditionally for medicinal purpose in Chinese, Ayurvedic, Persian and Unani medicines. The bioactive constituents such as apocarotenoids, monoterpenoids, flavonoids, phenolic acids and phytosterols are widely investigated in experimental and clinical studies for a wide range of therapeutic effects, especially on the nervous system. Some of the active constituents of saffron have high bioavailability and bioaccessibility and ability to pass the blood-brain barrier. Multiple preclinical and clinical studies have supported neuroprotective, anxiolytic, antidepressant, learning and memory-enhancing effect of saffron and its bioactive constituents (safranal, crocin, and picrocrocin). Thus, this plant and its active compounds could be a beneficial medicinal food ingredient in the formation of drugs targeting nervous system disorders. This review focuses on phytochemistry, bioaccessibility, bioavailability, and bioactivity of phytochemicals in saffron. Furthermore, the therapeutic effect of saffron against different nervous system disorders has also been discussed in detail.

Fruits contain enormous source of vitamins that provides energy to the human body. These are also affluent in essential and vital vitamins, minerals, fiber, and health-promoting components, which has led to an increase in fruit consumption in recent years. Though fruit consumption has expanded considerably in recent years, the use of synthetic chemicals to ripen or store fruits has been steadily increasing, resulting in postharvest deterioration. Alternatives to synthetic chemicals should be considered to control this problem. Instead of utilizing synthetic chemicals, this study suggests using natural plant products to control postharvest decay. The aim of this study indicates how natural plant products can be useful and effective to eliminate postharvest diseases rather than using synthetic chemicals. Several electronic databases were investigated as information sources, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE, and CNKI Scholar. The current review focused on the postharvest of fruits has become more and more necessary because of these vast demands of fruits. Pathogen-induced diseases are the main component and so the vast portion of fruits get wasted after harvest. Besides, it may occur harmful during harvesting and subsequent handling, storage, and marketing and after consumer purchasing and also causes for numerous endogenous and exogenous diseases via activating ROS, oxidative stress, lipid peroxidation, etc. However, pathogenicity can be halted by using postharvest originating natural fruits containing bioactive elements that may be responsible for the management of nutritional deficiency, inflammation, cancer, and so on. However, issues arising during the postharvest diseases must be controlled and resolved before releasing the horticultural commodities for commercialization. Therefore, the control of postharvest pathogens still depends on the use of synthetic fungicides; however, due to the problem of the development of the fungicide-resistant strains there is a good demand of public to eradicate the use of pesticides with the arrival of numerous diseases that are expanded in their intensity by the specific chemical product. By using of the organic or natural products for controlling postharvest diseases of fruits has become a mandatory step to take. In addition, antimicrobial packaging may have a greater impact on long-term food security by lowering the risk of pathogenicity and increasing the longevity of fruit shelf life. Taken together, natural chemicals as acetaldehyde, hexanal, eugenol, linalool, jasmonates, glucosinolates, essential oils, and many plant bioactive are reported for combating of the postharvest illnesses and guide to way of storage of fruits in this review.

Background The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer's onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. Objective The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. Methods The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11-7082. Results The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381-452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range -9.99±0.8 to -34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. Conclusion This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.

Heterophragma adenophyllum (HA) is an important medicinal plant which is used in traditional medicine for the treatment of muscular tension and pain. Herein, we report the isolation of methyl,1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylate (1), from the roots of H. adenophyllum. The isolated compound 1 was evaluated for in vivo muscle relaxant, sedative, and analgesic potential in Swiss albino mice. Results revealed that the isolated compound 1 exhibited a dose- and time-dependent muscle coordination (51%) and a significant (p p 1. Furthermore, the experimental results were compared with the theoretical studies by using density functional theory (DFT). The stability of the compound as well as the flow of electrons was determined by the calculated Frontier orbital analysis. The calculated stretching frequencies, 1H-NMR/13C-NMR chemical shift values and UV-visible spectra were found to be in agreement with experimental values. The results obtained from molecular docking studies were used to explore the mechanism of analgesic and muscle relaxant activity. Communicated by Ramaswamy H. Sarma

Lung cancer is a leading cause of cancer-associated death in all over the globe. This study was undertaken to determine the expression and interaction of membrane-bound receptors CD74 and CD44 in human lung adenocarcinoma cells and their associated signaling was also attempted. Levels of CD74 and CD44 were studied in human lung adenocarcinoma-evolved cells A549 and H460. CD74-mediated downstream signaling was studied by the nuclear-transcription-factor NF-κB and prostaglandin E (PGE) production. Flow-cytometric analysis showed that both CD74 and CD44 were perfectly expressed in A549 cells. Importantly, Western immunoblotting showed that A549 cells expressed only two isoforms of CD74 at 33 and 35 kDa but isoform at 41 kDa was absent. These results were verified in H460 cells. Confocal microscopy showed CD74 and CD44 was colocalized but heterotypic interaction between them was missing in both A549 and H460 cells. Activation of NF-κB and production of PGE in human lung cancer cells were comparable with other cancer cells. In conclusion, this is the first study that shows A549 and H460 cells expressed two distinctive isoforms of CD74 but isoform at 41 kDa was absent. Due to the absence of this isoform, the direct physical interaction between them CD74 and CD44 was lacking. Furthermore, the data also demonstrated that lacking of direct physical interaction between CD74 and CD44 had no effect on NF-κB activation and PGE production indicating that CD74-mediated downstream signaling occurs either through coreceptors or indirect interaction with CD44 in human lung cancer cells. Abbreviation: CD: cluster of differentiation; SCLC: small cell lung cancer; NSCLC: nonsmall cell lung cancer; SCC: squamous cell carcinoma; ADC: adenocarcinoma; LCC: large cell carcinoma.

BackgroundAnalgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product fromDiospyros lotus, was tested for the aforementioned bioactivities.ObjectivesTo evaluate analgesic, anti-inflammatory, and sedative potential ofD. lotusextracts in animal paradigms using BALB/c mice as experimental model.MethodsAnalgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction ofD. lotuswere evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound1. Compound1was also subjected to molecular modeling studies against cyclooxygenase enzymes.ResultsResults from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p 1forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor.ConclusionsCompound1exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use ofD. lotusin the treatment of inflammation, pain, and insomnia.

Diospyros lotus, also known as date-plum, belongs to theEbenaceaefamily and is mostly recognized as a rootstock forD.kaki. Similar classes of naphthoquinones inD.lotusare investigated against cancer and inflammation and have antimicrobial, sedative, and analgesic properties. Six chemical constituents (1-6) were isolated fromDiospyros lotusand tested for anti-inflammatory effects at the dose of 2.5 and 5 mg/kg, i.p., using carrageenan (1%, 0.05 ml)-induced paw edema. The maximum protection against carrageenan-induced edema was observed for compounds 1 and 2. Both studied compounds demonstrated significant anti-inflammatory effect after the 3rdhour of posttreatment. The maximum anti-inflammatory effect of compound 1 was 85.96%, while that of compound 2 was 81.44%, followed by compounds 5 and 6, which exhibited 80.11% and 82.45% effect, respectively. Similarly, histamine-induced inflammation was significantly antagonized by 1, 2, 5, and 6 with 87.99%,82.18±1.8,80.40±1.59, and 77.44% effects, respectively, at 5 mg/kg after the 2ndhour of posttreatment. The rest of the tested compounds did not show any significant effect as compared to the negative control. Interestingly, no toxicity was observed at higher doses. Moreover, the extracted compounds showed remarkable antibacterial activity against the Gram-positive bacteria and no effect against the Gram-negative bacteria. Docking studies on target cyclooxygenases showed that all the compounds established interactions with the key amino acid residues present in the additional pocket of COX-2. Hence, these compounds may act as selective COX-2 inhibitors. In conclusion, the findings of the current study suggest that the roots ofDiospyros lotusmay contain some anti-inflammatory and antibacterial agents with minimal toxicological effects and accordingly this plant product is recommended for further investigations.

Patients treated with cyclophosphamide (CP) usually suffer from severe hemorrhagic cystitis (HC). Our previous study exhibited that mesna + celery cotherapy partially ameliorated HC. Therefore, there is a substantial need to seek alternative regimens to get complete protection against CP-induced HC. The current study investigated the effects of mesna + celery seed oil (MCSO) or mesna + manuka honey (MMH) cotherapy against CP-induced HC in adult male rabbits. The forty rabbits were divided into four equal groups and treated for three weeks. The control group (G1) received distilled water and the second group (G2) received CP (50 mg/kg/week). The third group (G3) received CP + MCSO (CPMCSO regimen), and the fourth group (G4) received CP + MMH (CPMMH regimen). The urinary bladder (UB) specimens were processed to evaluate UB changes through histopathological, immunohistochemical, ultrastructural, and biochemical investigations. In G2, CP provoked HC features (urothelial necrosis, ulceration, and sloughing), UB fibrosis, and TNF-α immunoexpression. Besides, CP reduced the activity of antioxidant enzymes (GPx1, SOD3, and CAT) and elevated the serum levels of NF-κB, TNF-α, IL-1B, and IL-6 cytokines in G2 rabbits. In contrast, the CPMMH regimen caused significant increments of UB protection against HC in G4 rabbits compared to the partial protection by the CPMCSO regimen in G3. Therefore, our study indicated for the first time that the novel CPMMH regimen resulted in complete UB protection against CP-induced HC via combined antioxidant, anti-inflammatory, and antifibrotic properties.

There is a need to synthesize eco-friendly nanoparticles with more effective and potent antibacterial activities. A green and cost-effective method for the synthesis of silver nanoparticles (AgNPs) using Thymus vulgaris, Mentha piperita, and Zingiber officinale extracts was developed. The analytical instrumentation, namely, UV/Vis, absorption spectroscopy, FTIR, and scanning electron microscopy (SEM), was used to determine the developed AgNPs, confirming the functional groups involved in their reduction. Acidic molybdate, DPPH, and FRAP regents were reacted with AgNPs extract to evaluate their antioxidant, scavenging, and oxidative activities. The agar well diffusion method was used to determine the antibacterial potential of AgNPs extracts using clinical isolates. The developed AgNPs showed peaks at 25 cum\Diff, 50 cum\Diff, and 75 cum\Diff, respectively, of 16.59 ± 0.78, 45.94 ± 1.07, and 81.04 ± 0.98 nm, for Thymus vulgaris, Mentha piperita, and Zingiber officinale. SEM revealed uniform prepared and encapsulated AgNPs by plant extracts matrix. The FTIR shows the involvement of amide (-CO-NH2), carbonyl (-CO), and hydroxyl (-OH), which resulted in the reduction of AgNPs. The AgNPs extract showed significantly higher TAA, DPPH, and FRAP values than free AgNPs and plant extract ( p < 0.05 ). Antibacterial of AgNPs extracts revealed various degrees of inhibition zones against Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. The developed AgNPs extract showed acceptable antioxidant activities and noticeable antibacterial potential. The prepared green synthesized AgNPs showed a promising antibacterial activity against four multidrug-resistant clinical isolates, Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. Further, fractionated extracts other than crude extracts will be utilized in the preparation of AgNPs to get more efficient antibacterial activities for future work.

Rhazya stricta is a well-known medicinal plant and source of numerous potential secondary metabolites including steroids, alkaloids, and tannins. R. stricta possesses multimedical applications and used for curing of various diseases such as inflammation, diabetes, sore throat, infectious, helminthiasis, arthritis, and cancer. The current investigation deals with synthesizing AgNPs using aqueous and ethanol extracts of R. stricta. The synthesized R. stricta-AgNPs were characterized through UV-visible, Fourier transform infrared (FTIR), and atomic force microscopy (AFM) methods. The UV-visible analysis exhibited a characteristic absorption λ max at 475 nm in R. stricta ethanol AgNPs while this peak was absent in R. stricta aqueous crude extract. The thermal stability of R. stricta-AgNPs demonstrated that by increasing the reduction time and temperature, the absorption of AgNPs also increased, leading to more stable NPs formation. The FTIR spectra showed a broad peak at 450-550 cm-1 that confirmed the occurrence of AgNPs of R. stricta. The AFM study of the synthesized AgNPs revealed the spherical shape and size ranging from 30 nm to 90 nm. In antioxidant and antibacterial study, the R. stricta-AgNPs exhibited good antioxidant activity (87.94% and 88.37%) than the ethanol crude extract (50.00% and 56.81%) at 100 μg/mL using DPPH assay. Maximum antibacterial activity was recorded against Gram-positive bacteria (Staphylococcus aureus), which was 15 and 0 mm, while against Gram-negative bacteria (Klebsiella pneumonia) was found to be 16 and 14 mm, respectively, whereas against Bacillus subtills, a poor activity was recorded as 14 for extract and 0 mm for AgNPs, respectively. In the acetic acid-induced writhing model, the percent effect of extract (100 mg/kg) and AgNPs (15 mg/kg) was 79.98 and 83.23, respectively. The maximum muscle coordination effect of extracts in the inclined plan and traction test was 44% and 38% at higher doses. A mild sedative effect was also recorded against extract and AgNPs. The significant ( p < 0.05 ) effect of extract was noted at 100 mg/kg while AgNPs was more significant ( p < 0.01 ) at the tested dose of 15 mg/kg. These findings have concluded that R. stricta-AgNPs is an effective bioreductant of AgNPs synthesis and exhibit several applications in distinctive biomedical and pharmaceutical industries.

Euphorbia pulcherrima is an important medicinal plant that is used in a traditional system for its curative properties such as analgesic potency, antipyretic, anti-inflammatory, sedation potential, and antidepressant and cure of diseases such as skin diseases. This study deals with the isolation of two flavonoids namely spinacetin (1) and patuletin (2) from chloroform fraction of Euphorbia pulcherrima. The isolated compound spinacetin (1) and patuletin (2) were screened for in vivo anti-inflammatory, analgesic, sedative, and muscle relaxant effects. Compounds 1 and 2 were assessed against hot plate-induced noxious stimuli at various doses which showed excellent ( p < 0.05 ) analgesic effect in a dose-dependent manner. The muscle relaxant activity was determined by traction and inclined screening model, both compounds showed significant muscle relaxant activity with time. The sedative potential of isolated compounds 1 and 2 was determined by the open field model, both compounds showed good sedation ( p < 0.05 ) at 20 mg/kg. The anti-inflammatory potential of compound 1 was recorded by histamine-induced paw edema and carrageen paw edema model, and in both models, compounds 1 and 2 showed strong effect at 20 mg/kg. Binding orientations, binding energy values, and computed inhibition constants (Ki) values revealed that the studied compounds have a good to excellent inhibition potential against μ-opioid receptors and COX-2.

In the present study, gold (Au) and silver (Ag) nanoparticles (NPs) were synthesized from aqueous extracts of Opuntia dillenii, characterized by various advanced techniques and investigated for antibacterial and antifungal potential. Phytochemical screening of O. dillenii showed the presence of alkaloids, betacyanin, saponins, tannins, flavonoids, and phlobatannins. The characterizations of the synthesized metal NPs were performed such as UV-visible spectrophotometer, FTIR (Fourier transform infrared) spectrophotometer, SEM (scanning electron microscopy) and EDX (energy-dispersive X-ray). Through the application of such advance techniques, the UV-visible spectrophotometer showed the bands of absorbance for AgNPs and AuNPs at 420 nm and 525 nm range, respectively. The FTIR spectra for both and AgNPs also appeared in the range of 4000-400 cm-1. SEM was performed for the textural and morphological characteristics of the NPs such as shape, size distribution, and surface structure. Elemental analysis was recorded for the synthesis of Au and AgNPs, which confirmed its purity. The O. dillenii extract and their synthesized Au and AgNPs showed a clear zone of inhibition against the E. coli, S. aureus, K. pneumonia, and P. aeruginosa bacteria and T. viride, C. albicans, C. krusei, and A. niger fungal species.

Edible lotus (