Contemporary approaches in the management of uterine leiomyomas.

BACKGROUND: Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention. OBJECTIVE: Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas. SEARCH STRATEGY: PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA). RESULTS: Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas. CONCLUSION: Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.

Withania somnifera - a magic plant targeting multiple pathways in cancer related inflammation.

BACKGROUND: Deregulated inflammatory responses are known to play a pivotal role in cancer initiation and progression. Tumor microenvironment is associated with the presence of a diverse array of inflammatory reactions, which further help tumor growth, metastasis and drug resistance. Withania somnifera is known to curb proliferation of cancer cells and lower inflammatory responses. PURPOSE: In order to minimize the inflammation, cancer treatments often include immunomodulatory drugs. However, given the side effects of both of the cytotoxic cancer drugs and synthetic immunomodulatory agents, there is a need to develop novel anti-inflammatory agents for improved cancer therapy. A number of reports indicate that bioactive phytochemicals derived from W. somnifera exhibit anti-inflammatory capabilities in cancer. A deeper look into the underlying molecular mechanisms implicated in W. somnifera mediated anti inflammation is lacking, which is essential to fully understand the potential of this magical plant in cancer. Therefore, in the present review we are summarizing various reports, which describe mechanistic understanding of W. somnifera in cancer related inflammation. STUDY DESIGN AND METHODOLOGY: In order to gather information on the molecular pathways affected by W. somnifera in cancer related inflammation, 'PubMed' and 'Science Direct' databases were searched using keywords Withania, cancer inflammation, and Withaferin A. Selected literature was analyzed to cover the role of inflammation in cancer, usage and side effects of anti-inflammatory drugs, W. somnifera as an immunomodulatory agent in cancer, molecular pathways modulated by W. somnifera in various preclinical models, and clinical trials using W. somnifera as an anti-inflammatory agent. RESULTS: Upon literature survey we found that both W. somnifera extracts and Withaferin-A, exhibit anti inflammatory activities in various preclinical cancer models. W. somnifera modulates a number of signaling pathways such as NF-kB, JAK-STAT and AP1 to reduce cancer related inflammation. Anti inflammatory properties of W. somnifera might be effective in the treatment of drug resistance in cancers. Based on its promising effects against cancer associated inflammation in preclinical studies, W. somnifera derived products are being tested in clinical trials. CONCLUSION: Several preclinical studies demonstrated anti-inflammatory potential of W. somnifera in a variety of cancers. While a few clinical trials are investigating the role of W. somnifera in various diseases, focused studies on its role in cancer related inflammation are lacking. Additionally, its anti-inflammatory effects offer targeting of senescence associated secretory phenotype (SASP), which is speculated to play a critical role in chemoresistance. Apart from targeting cancer cell proliferation, anti-inflammatory effects of Withania provide double advantage in cancer management. Therefore, clinical trials to target cancer related inflammation using W. somnifera as a drug, should be performed to validate its advantages in cancer therapy.

Drug Screening Assays on Medulloblastoma Stem Cells Using Compound Libraries.

Conventional chemotherapies for medulloblastoma are restricted to only proliferative population leaving the cancer stem cells unscathed. This shortcoming of the traditional therapies is attributed to the relapse and metastasis of the cancer. The current research is entirely focused on the screening of therapeutic agents that can restrict and target the self-renewal potential of the cancer stem cells. The advances in drug screening strategies have led to high-throughput screening which provide a robust and expeditious platform to screen potential compounds against cancer stem cells. In this book chapter, we describe two in vitro assays that are routinely used to measure the cell killing and anti-self-renewal activity of the compounds against the cancer stem cells. Combining these assays with high-throughput screening offers a rapid, reliable, and inexpensive approach to screen potential compounds against cancer stem cells and to overcome the limitation of conventional chemotherapeutic agents.

Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants - Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) - a molecular docking study.

COVID-19 (Coronavirus disease 2019) is a transmissible disease initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) since 31st December 2019 in Wuhan city of China and the infection has outspread globally influencing millions of people. Here, an attempt was made to recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular docking and molecular dynamics (MD) simulation study. Molecular docking study showed six probable inhibitors against SARS-CoV-2 Mpro (Main protease), two from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]), one from Tinospora cordifolia (Giloy) (Tinocordiside [8.10 kcal/mol]) and three from Ocimum sanctum (Tulsi) (Vicenin [8.97 kcal/mol], Isorientin 4'-O-glucoside 2″-O-p-hydroxybenzoagte [8.55 kcal/mol] and Ursolic acid [8.52 kcal/mol]). ADMET profile prediction showed that the best docked phytochemicals from present work were safe and possesses drug-like properties. Further MD simulation study was performed to assess the constancy of docked complexes and found stable. Hence from present study it could be suggested that active phytochemicals from medicinal plants could potentially inhibit Mpro of SARS-CoV-2 and further equip the management strategy against COVID-19-a global contagion. HighlightsHolistic approach of Ayurvedic medicinal plants to avenge against COVID-19 pandemic.Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) predicted to significantly hinder main protease (Mpro or 3Clpro) of SARS-CoV-2.Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine, Tinocordiside, Vicenin, Ursolic acid and Isorientin 4'-O-glucoside 2″-O-p-hydroxybenzoagte were anticipated to impede the activity of SARS-CoV-2 Mpro.Drug-likeness and ADMET profile prediction of best docked compounds from present study were predicted to be safe, drug-like compounds with no toxicity.Communicated by Ramaswamy H. Sarma.

Naturally Occurring Bioactives as Antivirals: Emphasis on Coronavirus Infection.

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.

Stimuli responsive and receptor targeted iron oxide based nanoplatforms for multimodal therapy and imaging of cancer: Conjugation chemistry and alternative therapeutic strategies.

Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.

Microbiome and host crosstalk: A new paradigm to cancer therapy.

The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.

Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs.

In recent years, there have been significant advancements in the nanotechnology for cancer therapy. Even though molybdenum disulphide (MoS2)-based nanocomposites demonstrated extensive applications in biosensing, bioimaging, phototherapy, the review article focusing on MoS2 nanocomposite platform has not been accounted for yet. The review summarizes recent strategies on design and fabrication of MoS2-based nanocomposites and their modulated properties in cancer treatment. The review also discussed several therapeutic strategies (photothermal, photodynamic, immunotherapy, gene therapy and chemotherapy) and their combinations for efficient cancer therapy along with certain case studies. The review also inculcates various diagnostic techniques viz. magnetic resonance imaging, computed tomography, photoacoustic imaging and fluorescence imaging for diagnosis of cancer.

Eco-friendly decolorization and degradation of reactive yellow 145 textile dye by Pseudomonas aeruginosa and Thiosphaera pantotropha.

Dyes are toxic and inherently resistant to microbial degradation. In this study, decolorization and degradation of textile dye reactive yellow 145 (RY145) were evaluated using pure bacterial strains Pseudomonas aeruginosa (RS1) and Thiosphaera pantotropha ATCC 35512. In nutrient broth under static condition, complete decolorization of 50 mg L-1 RY145 could be achieved within 96 h and 72 h, for Pseudomonas aeruginosa (RS1) and Thiosphaera pantotropha, respectively. In contrast, under shaking condition both the cultures could achieve only 50% decolorization in 96 h. Treatment under sequential static and shaking condition resulted in complete decolorization and 65% mineralization after 96 h. Higher dye concentration in excess of 100 mg L-1 and 50 mg L-1 decreased the extent of dye mineralization in Pseudomonas aeruginosa and Thiosphaera pantotropha, respectively. Even with the repetitive addition of the dye, both the strains were capable of decolorizing the dye. Acclimatized cultures showed 54% decolorization of RY145 in mineral media (MM) even in the absence of a readily degradable external carbon source. Amongst various individual carbon and nitrogen sources, maximum decolorization was observed in MM supplemented with peptone as carbon and nitrogen source at pH 7 under static condition.

Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials.

In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-α, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity.

Revisiting eukaryotic anti-infective biotherapeutics.

Emerging drug resistance has forced the scientific community to revisit the observational data documented in the folklore and come up with novel and effective alternatives. Candidates from eukaryotic origin including herbal products and antimicrobial peptides are finding a strategic place in the therapeutic armamentarium against infectious diseases. These agents have recently gained interest owing to their versatile applications. Present review encompasses the use of these alternative strategies in their native or designer form, alone or in conjunction with antibiotics, as possible remedial measures. Further to this, the limitations or the possible concerns associated with these options are also discussed at length.

Synthesis and evaluation of some new substituted benzothiazepine and benzoxazepine derivatives as anticonvulsant agents.

A new series of 4-(4'-Hydroxyphenyl)-2-(3-substitutedphenyl)-3-(4-substitutedphenylamino methylene)-2,3-dihydro-1,5-benzothiazepines (3a-3j) and 4-(4'-Hydroxyphenyl)-2-(3-substituted phenyl)-3-(4-substitutedphenylaminomethylene)-2,3-dihydro-1,5-benzoxazepins (3a'-3j') were synthesized and evaluated for their anticonvulsant activity. All these compounds were screened in vivo, for their anticonvulsant activity and acute toxicity. Compound 3g was found to be most potent compound of this series and was compared with the reference drug phenytion sodium. The structures of these compounds have been established by IR, (1)H NMR and (13)C NMR spectroscopic data.

Synthesis of substituted acridinyl pyrazoline derivatives and their evaluation for anti-inflammatory activity.

A rapid preparation of compounds (1-24), with the objective of discovering novel and potent anti-inflammatory agent. All the compounds exhibited anti-inflammatory and analgesic activities at the dose 50 mg/kg p.o. The compound 1-(2',4'-Chloroacridine-9'-yl)-3-(5'-pyridine-4-yl)-(1,3,4-oxadiazol-2-yl-thiomethyl)-pyrazole-5-one 24 showed better anti-inflammatory and analgesic activities at the three graded dose of 25, 50 and 100 mg/kg p.o.