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Recently, malignant neoplasms have growingly caused human morbidity and mortality. Head and neck cancer (HNC) constitutes a substantial group of malignancies occurring in various anatomical regions of the head and neck, including lips, mouth, throat, larynx, nose, sinuses, oropharynx, hypopharynx, nasopharynx, and salivary glands. The present study addresses the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway as a possible therapeutic target in cancer therapy. Finding new multitargeting agents capable of modulating PI3K/Akt/mTOR and cross‐linked mediators could be viewed as an effective strategy in combating HNC. Recent studies have introduced phytochemicals as multitargeting agents and rich sources for finding and developing new therapeutic agents. Phytochemicals have exhibited immense anticancer effects, including targeting different stages of HNC through the modulation of several signaling pathways. Moreover, phenolic/polyphenolic compounds, alkaloids, terpenes/terpenoids, and other secondary metabolites have demonstrated promising anticancer activities because of their diverse pharmacological and biological properties like antiproliferative, antineoplastic, antioxidant, and anti‐inflammatory activities. The current review is mainly focused on new therapeutic strategies for HNC passing through the PI3K/Akt/mTOR pathway as new strategies in combating HNC. [ABSTRACT FROM AUTHOR]

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature‐driven phytochemical component, is a well‐known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti‐inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers. [ABSTRACT FROM AUTHOR]

Climate change is the most serious threat to agricultural productivity. Ethiopia's agricultural sector is affected by climate change. The northern part of Ethiopia is among the drought prone and topographically diversified areas. The purpose of this study was to examine the impact of climate change on crop yields, assess the pattern of rainfall maximum and lowest temperatures and assess the trajectory of selected crop yields. Historical weather station and National Aeronautics and Space Administration (NASA) power data were collected from 1981 to 2020. The Mann–Kendall (MK) trend test and Sen's slope (SS) method estimator were employed to estimate the trends and the direction of the trend. RClimDex package is used for climate extreme analysis. Nine rainfall and 11 temperature indices from a list of 27 extreme rainfall and temperature indices were used. The study found that the rainfall showed a significant decreasing and insignificant decreasing trend in Farta and Yilmana Densa districts, respectively. Maximum and minimum temperatures in both sites showed increasing trends. Rainfall happenings become more unanticipated, owing to the precipitation concentration index and anomaly trends. The majority of the indicators for extreme rainfall at both sites showed a downward trend. With the exception of the duration of cold spells, the annual lowest value of the daily minimum temperature, cold days and cold nights, the majority of the extreme temperature indices at both sites showed an increasing trend. The principal crop yields were connected with rainfall and temperature fluctuation, according to Pearson's product–moment correlation results, although the effects varied by crop and region. In summary, rising temperatures and decreasing precipitation may have a negative influence on agricultural activities, especially crop productivity. [ABSTRACT FROM AUTHOR]

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti‐aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2‐related factor 2 is a factor related to transcription with anti‐inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

The identification of agents that can reverse drug resistance in cancer chemotherapy, and enhance the overall efficacy is of great interest. Paclitaxel (PTX) belongs to taxane family that exerts an antitumor effect by stabilizing microtubules and inhibiting cell cycle progression. However, PTX resistance often develops in tumors due to the overexpression of drug transporters and tumor‐promoting pathways. Noncoding RNAs (ncRNAs) are modulators of many processes in cancer cells, such as apoptosis, migration, differentiation, and angiogenesis. In the present study, we summarize the effects of ncRNAs on PTX chemotherapy. MicroRNAs (miRNAs) can have opposite effects on PTX resistance (stimulation or inhibition) via influencing YES1, SK2, MRP1, and STAT3. Moreover, miRNAs modulate the growth and migration rates of tumor cells in regulating PTX efficacy. PIWI‐interacting RNAs, small interfering RNAs, and short‐hairpin RNAs are other members of ncRNAs regulating PTX sensitivity of cancer cells. Long noncoding RNAs (LncRNAs) are similar to miRNAs and can modulate PTX resistance/sensitivity by their influence on miRNAs and drug efflux transport. The cytotoxicity of PTX against tumor cells can also be affected by circular RNAs (circRNAs) and limitation is that oncogenic circRNAs have been emphasized and experiments should also focus on onco‐suppressor circRNAs. Highlights: Chemotherapy is still the main therapy for cancer patients.Paclitaxel (PTX) prevents the depolymerization of microtubules to induce cell cycle arrest.PTX exposure often leads to the emergence of resistance due to activation of various molecular pathways.MicroRNAs can have dual effects to suppress or induce PTX resistance by targeting different molecular pathways, such as STAT3, Wnt, or CDK6.Long noncoding RNAs affect PTX sensitivity mainly by sponging specific miRNAs.Circular RNAs regulate the response to PTX chemotherapy via affecting miRNAs and their downstream targets. [ABSTRACT FROM AUTHOR]

Increased inflammasome responses are strongly implicated in inflammatory diseases; however, their specific roles are incompletely understood. Therefore, we sought to examine the roles of nucleotide‐binding oligomerization domain–like receptor (NLR) family, pyrin domain–containing 3 (NLRP3) and absent in melanoma‐2 (AIM2) inflammasomes in cigarette smoke–induced inflammation in a model of experimental chronic obstructive pulmonary disease (COPD). We targeted NLRP3 with the inhibitor MCC950 given prophylactically or therapeutically and examined Aim2−/− mice in cigarette smoke–induced experimental COPD. MCC950 treatment had minimal effects on disease development and/or progression. Aim2−/− mice had increased airway neutrophils with decreased caspase‐1 levels, independent of changes in lung neutrophil chemokines. Suppressing neutrophils with anti‐Ly6G in experimental COPD in wild‐type mice reduced neutrophils in bone marrow, blood and lung. By contrast, anti‐Ly6G treatment in Aim2−/− mice with experimental COPD had no effect on neutrophils in bone marrow, partially reduced neutrophils in the blood and had no effect on neutrophils or neutrophil caspase‐1 levels in the lungs. These findings identify that following cigarette smoke exposure, Aim2 is important for anti‐Ly6G–mediated depletion of neutrophils, suppression of neutrophil recruitment and mediates activation of caspase‐1 in neutrophils. [ABSTRACT FROM AUTHOR]

Anticancer drugs are not purely effective because of their toxicity, side effects, high cost, inaccessibility, and associated resistance. On the other hand, cancer is a complex public health problem that could intelligently adopt different signaling pathways and alter the body's metabolism to escape from the immune system. One of the cancer strategies to metastasize is modifying pH in the tumor microenvironment, ranging between 6.5 and 6.9. As a powerful determiner, lactate is responsible for this acidosis. It is involved in immune stimulation, including innate and adaptive immunity, apoptotic‐related factors (Bax/Bcl‐2, caspase), and glycolysis pathways (e.g., GLUT‐1, PKM2, PFK, HK2, MCT‐1, and LDH). Lactate metabolism, in turn, is interconnected with several dysregulated signaling mediators, including PI3K/Akt/mTOR, AMPK, NF‐κB, Nrf2, JAK/STAT, and HIF‐1α. Because of lactate's emerging and critical role, targeting lactate production and its transporters is important for preventing and managing tumorigenesis. Hence, exploring and developing novel promising anticancer agents to minimize human cancers is urgent. Based on numerous studies, natural secondary metabolites as multi‐target alternative compounds with health‐promoting properties possess more high effectiveness and low side effects than conventional agents. Besides, the mechanism of multi‐targeted natural sources is related to lactate production and cancer‐associated cross‐talked factors. This review focuses on targeting the lactate metabolism/transporters, and lactate‐associated mediators, including glycolytic pathways. Besides, interconnected mediators to lactate metabolism are also targeted by natural products. Accordingly, plant‐derived secondary metabolites are introduced as alternative therapies in combating cancer through modulating lactate metabolism and glycolytic pathways. [ABSTRACT FROM AUTHOR]

Previous studies have recognized that the presence of academic directors on the board leads to better corporate governance and accounting quality. However, studies have yet to establish the effectiveness of academic directors in mitigating corporate expropriation in emerging markets. The purpose of this study is to investigate the effect of academic directors on corporate expropriation in Chinese listed firms. It is observed that the presence of the academic director in the board mitigates earnings management and abnormal investments and enhances the dividend payments. Additionally, we find that the critical mass of academic directors curbs the expropriator managerial behavior in Chinese listed firms. [ABSTRACT FROM AUTHOR]

The flare‐up in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that emerged in December 2019 in Wuhan, China, and spread expeditiously worldwide has become a health challenge globally. The rapid transmission, absence of anti‐SARS‐CoV‐2 drugs, and inexistence of vaccine are further exacerbating the situation. Several drugs, including chloroquine, remdesivir, and favipiravir, are presently undergoing clinical investigation to further scrutinize their effectiveness and validity in the management of COVID‐19. Natural products (NPs) in general, and plants constituents specifically, are unique sources for various effective and novel drugs. Immunostimulants, including vitamins, iron, zinc, chrysin, caffeic acid, and gallic acid, act as potent weapons against COVID‐19 by reinvigorating the defensive mechanisms of the immune system. Immunity boosters prevent COVID‐19 by stimulating the proliferation of T‐cells, B‐cells, and neutrophils, neutralizing the free radicals, inhibiting the immunosuppressive agents, and promoting cytokine production. Presently, antiviral therapy includes several lead compounds, such as baicalin, glycyrrhizin, theaflavin, and herbacetin, all of which seem to act against SARS‐CoV‐2 via particular targets, such as blocking virus entry, attachment to host cell receptor, inhibiting viral replication, and assembly and release. [ABSTRACT FROM AUTHOR]

The efficacy of chemotherapy in cancer therapy is limited due to resistance, treatment selectivity, and severe adverse effects. Immunotherapy, chemotherapy, targeted therapy, radiation, and surgery are the most common therapeutic strategies for treatment, with chemotherapy being the most successful. Nonetheless, these treatments exhibit poor effectiveness due to toxicity and resistance. Therefore, combination therapies of natural products may be used as an effective and novel strategy to overcome such barriers. Cisplatin is a platinum‐based chemotherapy agent, and when administered alone, it can lead to severe adverse effects and resistance mechanism resulting in therapeutic failure. Curcumin is a polyphenolic compound extracted from turmeric (Curcuma longa) exhibiting anticancer potential with minimal adverse effects. The combination therapy of curcumin and cisplatin is a novel strategy to mitigate/attenuate cisplatin‐related adverse effects and improve the barrier of resistance reducing unwanted effects. However, there are uncertainties on the efficacy of curcumin, and more in depth and high‐quality studies are needed. This review aims to explain the adverse effects related to individual cisplatin delivery, the positive outcome of individual curcumin delivery, and the combination therapy of curcumin and cisplatin from nano platform as a novel strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers. [ABSTRACT FROM AUTHOR]

Clinical investigations have characterized numerous disorders like autoimmune diseases, affecting the population at a rate of approximately 8–10%. These disorders are characterized by T‐cell and auto‐antibodies responses to self‐molecules by immune system reactivity. Several therapeutic options have been adopted in clinics to combat such diseases, however, most of them are recurring. Thus, the discovery of new effective agents for the treatment of autoimmune diseases is paramount. In this context, natural products might be a useful alternative to the current therapies. Plant alkaloids with their substantial therapeutic history can be particularly interesting candidates for the alleviation of autoimmune ailments. This review encompasses various alkaloids with significant effects against autoimmune diseases in preclinical trials. These results suggest further clinical assessment with respect to autoimmune illnesses. Furthermore, the application of modern technologies such as nanoformulation could be also helpful in the design of more effective therapies and thus further studies are needed to decipher their therapeutic efficacy as well as potential limitations. [ABSTRACT FROM AUTHOR]

Non-small-cell lung carcinoma (NSCLC) is one of the most lethal malignancies that include more than 80% of lung cancer cases worldwide. During the past decades, plants and plant-derived products have attracted great interest in the treatment of various human diseases. Curcumin, the turmeric isolated natural phenolic compound, has shown a promising chemo-preventive and anticancer agent. Numerous studies have shown that curcumin delays the initiation and progression of NSCLC by affecting a wide range of molecular targets and cell signalling pathways including NF-kB, Akt, MAPKS, BCL-2, ROS and microRNAs (miRNAs). However, the poor oral bioavailability and low chemical stability of curcumin remain as major challenges in the utilisation of this compound as a therapeutic agent. Different analogs of curcumin and new delivery systems (e.g., micelles, nanoparticles and liposomes) provided promising solutions to overcome these obstacles and improve curcumin pharmacokinetic profile. The present review focuses on current reported studies about anti-NSCLC effects of curcumin. NSCLC involved miRNAs whose expression is regulated by curcumin has also been discussed. Furthermore, recent researches on the use of curcumin analogs and delivery systems to enhance the curcumin benefits in NSCLC are also described. [ABSTRACT FROM AUTHOR]

Globally, approximately 12% of the population is inflicted by various types of urolithiasis. Standard treatments are available both to avert and treat urolithiasis, but with significant adverse side effects. Pentacyclic triterpenes represent a group of naturally occurring compounds which holds immense potential as therapeutic for treating kidney stone. This review aims to provide an integrative description on how pentacyclic triterpenes can effectively treat calcium oxalate urolithiasis through various mechanisms such as antioxidant, anti‐inflammatory, diuretic, and angiotensin‐converting enzyme inhibition. Some of the pentacylic triterpenes which shows promising activities include lupeol, oleanolic acid, betulin, and taraxasterol. Moreover, future perspectives in the development of pentacyclic triterpenes in formulations/drugs for urinary stone prevention are highlighted. It is anticipated that compiled information would serve as a scientific baseline to advocate further investigations on the potential of pentacyclic triterpenes in urolithiasis remediation. [ABSTRACT FROM AUTHOR]

Antiplatelet drugs reduce the risks associated with atherothrombotic events and show various applications in diverse cardiovascular diseases including myocardial infarctions. Efficacy of the current antiplatelet medicines including aspirin, clopidogrel, prasugrel and ticagrelor, and the glycoprotein IIb/IIIa antagonists, are limited due to their increased risks of bleeding, and antiplatelet drug resistance. Hence, it is important to develop new effective antiplatelet drugs, with fewer side‐effects. The vast repertoire of natural peptides can be explored towards this goal. Proteins and peptides derived from snake venoms and plants represent exciting candidates for the development of novel and potent antiplatelet agents. Consequently, this review discusses multiple peptides that have displayed antiplatelet aggregation activity in preclinical drug development stages. This review also describes the antiplatelet mechanisms of the peptides, emphasizing the signaling pathways intervened by them. Also, the hurdles encountered during the development of peptides into antiplatelet drugs have been listed. Finally, hitherto unexplored peptides with the potential to prevent platelet aggregation are explored. [ABSTRACT FROM AUTHOR]

Objective: Pyrus pashia has traditionally been used as a therapeutic agent including sedative. In this regard, hydroethanolic extract of Pyrus pashia (HEPP) was screened for phytochemical investigation, acute toxicity, and sedative-hypnotic activity to provide a scientific rationale to its ethno-medicinal uses.Methods: Mice were used in acute toxicity test; sedative potential was observed in open field test while thiopental-induced sleeping time and barbiturate-induced sleeping time tests were used for the assessment of hypnotic like effects of HEPP. Various phytochemical groups were detected in preliminary phytochemical tests.Results: In acute toxicity study, the extract was found safe up to 1g/kg while the extract caused 50% death at 1500 mg/kg. In all animal models, the extract had shown sedative and hypnotic effects but the most significant effect observed at increased dose in comparison with standard diazepam-treated group. In open field test, the extract at doses of 200 and 400 mg/kg, there is mild decrease in number of lines crossed by tested animals (mice) while significant reduction shown at 600 mg/kg compared with diazepam-treated group at dose 0.5 mg/kg. In phytochemical investigation HEPP subjected to different phytochemical tests. From the thoroughly study, it is revealed that these constituents mainly participating in sedation and hypnosis.Conclusions: The results of the present study showed significant sedative-hypnotic effects of the HEPP in mice and that the central benzodiazepine receptors are involved in the sedative-hypnotic effects of this plant. [ABSTRACT FROM AUTHOR]

Declining soil fertility and crop yields are common in arid and semi-arid areas. Sustainable technologies that halt or reverse this trend are required to ensure food security. The use of compost for soil amendment should build soil resilience to drought. However, manure (which is a raw material in compost production) is used as a fuel in many semiarid regions of the world. To encourage farmers to change from using manure or composts as fuel to adopting them as soil additives, it will be necessary to demonstrate the production benefits associated with such additives. A 2-yr field experiment was conducted in a semi-arid (steppe) desert environment in Pakistan on sandy-loamy soils. Poultry manure compost (PMC), pressmud compost (PrMC), and urea (U) were compared in a maize-maize (Zea mays L.) cropping system. The PMC and PrMC application increased soil organic carbon (SOC) and N as well as the soil's moisture content, but decreased the soil electrical conductivity (ECe) and pH after 2 yr. Replacing 25% of the U with PMC increased the mineral N and mean crop growth rate by 46%, the net assimilation rate by 30% and the yield by 219%, compared to the control. These results were comparable to applications of U alone and PMC with urea in a 25:75 application ratio. These results demonstrate that in semiarid regions, adding manure or compost as a soil additive improves the soil's yield potential. [ABSTRACT FROM AUTHOR]

This study examines the relationship between transformational leadership and organizational performance by evaluating the mediatory role of corporate social responsibility (CSR) and organizational innovation which has received considerably less attention in the literature. This study introduces CSR and organizational innovation as potential mediators of relationships between the key constructs of transformational leadership and organizational performance. Sufficient direct and mediation effects of predictors were tested using partial least squares structural equation modelling (PLS‐SEM) with data from 396 French firms. Sufficient configurations of the predictors indicating high and low scores of performance were explored using fuzzy set qualitative comparative analysis (fsQCA). The PLS‐SEM results show that both direct and indirect effects of transformational leadership on performance are significant. The fsQCA results reveal that a combination of CSR and transformational leadership leads to high performance. Alternately, high performance results from high innovation. This empirical study contributes to the current knowledge by applying both symmetrical and asymmetrical approaches to indicate performance at an organizational level. This study discusses the findings and provides theoretical, managerial, and research implications. [ABSTRACT FROM AUTHOR]

Polygonatum verticillatum is commonly used for the treatment of asthma and inflammation. The current study was aimed to scrutinize the pharmacological profile of methanolic extract of the aerial parts (PA). Isolated tracheal preparations were used for the evaluation of bronchodilatory activity, whilst the in vivo carrageenan-induced paw oedema test and an in vitro lipoxygenase (LOX) inhibitory assay were used for the assessment of the anti-inflammatory profile of PA. When tested against carbachol and K+ (80 mM)-induced contractions, PA caused complete inhibition of isolated rabbit tracheal preparations in a dose-dependent mode, similar to verapamil. While elucidating possible mechanism, PA shifted the Ca2+ concentration-response curves to the right, analogous to that produced by verapamil, confirming a Ca2+ channel blocker-like activity. PA provoked profound reduction in paw oedema with a maximum protection of 60.87% at 200 mg/kg i.p. in a dose-dependent manner which was augmented by its prominent LOX inhibitory activity (IC50: 125 µg/mL). These findings authenticated its therapeutic potential in the treatment of asthmatic and inflammatory conditions. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The current study was undertaken to explore the antipyretic and anticonvulsant profile of the Polygonatum verticillatum in established pharmacological paradigms. The crude methanol extract of rhizomes (PR) and aerial parts (PA) of the plant were tested in Brewer's-yeast-induced pyrexia and pentylenetetrazole-induced convulsion test. PR and PA both evoked prominent antipyretic activity ( p < 0.01) in a dose-dependent manner during all assessment times at the dose of 50, 100, and 200 mg/kg intraperitoneally. The protection elicited by PR (82.20%) at 200 mg/kg was comparable with aspirin (88.48%) as a standard drug at 100 mg/kg. However, PA was less potent, and maximum protection was 64% at 200 mg/kg. Both PR and PA were devoid of any anticonvulsant activity. Our results demonstrated prominent evidence of antipyretic activity of P. verticillatum that is consistent with the folk uses of the plant. In addition from a biodiversity point of view, PA of the plant can also be used as an alternate of PR. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]