Current updates on the epidemiology,pathogenesis and development of small molecule therapeutics for the treatment of Ebola virus infections

Ebola virus disease(EVD)is a rare,highly contagious and a deadly disease with a variable fatality rate ranging from 30%to 90%.Over the past two decades,Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo(DRC),and Uganda.The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus(ZEBOV),Sudan Ebolavirus(SUDV)and Bundibugyo Ebolavirus(BDBV).In recent years,significant strides have been made in therapeutic interventions.Notably,the US Food and Drug Administration has approved two monoclonal antibodies:InmazebTM(REGN-EB3)and Ansuvimab or EbangaTM.Additionally,many small molecules are currently in the developmental stage,promising further progress in medical treatment.Addressing the critical need for preventive measures,this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno(Ad26.ZEBOV)and Mvabea(MVA-BN-Filo)as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies.These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease.The current treatment landscape for EVD encompasses both nutritional(supportive)and drug therapies.The review comprehensively details the origin,pathogenesis,and epidemiology of EVD,shedding light on the ongoing efforts to combat this devastating disease.It explores small molecules in various stages of the development,discusses patents filed or granted,and delves into the clinical and supportive therapies that form the cornerstone of EVD management.This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention,treatment,and control of EVD.

A review on therapeutic potential of Nigella sativa:A miracle herb

Nigella sativa(N.sativa)(Family Ranunculaceae)is a widely used medicinal plant throughout the world.It is very popular in various traditional systems of medicine like Unani and Tibb,Ayurveda and Siddha.Seeds and oil have a long history of folklore usage in various systems of medicines and food.The seeds of N.saliva have been widely used in the treatment of different diseases and ailments.In Islamic literature,it is considered as one of the greatest forms of healing medicine.It has been recommended for using on regular basis in Tibb-e-Nabwi(Prophetic Medicine).It has been widely used as antihypertensive,liver tonics,diuretics,digestive,anti-diarrheal,appetite stimulant,analgesics,anti-bacterial and in skin disorders.Extensive studies on N.sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic,anticancer,immunomodulator,analgesic,antimicrobial,anti-inflammatory,spasmolytic,bronchodilator,hepato-protective,renal protective,gaslro-prolective,antioxidant properties,etc.Due to its miraculous power of healing,N.sativa has got the place among the top ranked evidence based herbal medicines.This is also revealed that most of the therapeutic,properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil.The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics,chemical composition and pharmacological activities of the seeds of this plant.

Essential oils used in aromatherapy: A systemic review

Nowadays, use of alternative and complementary therapies with mainstream medicine has gained the momentum. Aromatherapy is one of the complementary therapies which use essential oils as the major therapeutic agents to treat several diseases. The essential or volatile oils are extracted from the flowers, barks, stem, leaves, roots, fruits and other parts of the plant by various methods. It came into existence after the scientists deciphered the antiseptic and skin permeability properties of essential oils. Inhalation, local application and baths are the major methods used in aromatherapy that utilize these oils to penetrate the human skin surface with marked aura. Once the oils are in the system, they remodulate themselves and work in a friendly manner at the site of malfunction or at the affected area. This type of therapy utilizes various permutation and combinations to get relief from numerous ailments like depression, indigestion, headache, insomnia, muscular pain, respiratory problems, skin ailments, swollen joints, urine associated complications etc. The essential oils are found to be more beneficial when other aspects of life and diet are given due consideration. This review explores the information available in the literature regarding therapeutic, medical, cosmetic, psychological, olfactory, massage aromatherapy, safety issues and different plants used in aromatherapy. All the available information was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubM ed, Science Direct, Web of Science, and library search.

Estimation of total phenolic content,in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera

Objective:To evaluate and compare the antioxidant potential and anti-inflammatory activity of ethanolic extract of flowers of Moringa oleifera(M.oleifera)grown in Oman.Methods:Flowers of M.oleiferawere collected in the month of December 2012 and identified by a botanist.Alcoholic extract of the dry pulverized flowers ofM.oleiferawere obtained by cold maceration method.The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods.Folin-Ciocalteu reagent was used to estimate total phenolic content.DPPH was used to determinein-vitroantioxidant activity and anti-inflammatory activity of flowers was investigated by protein denaturation method.Results:Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins,alkaloids,flavonoids,cardiac glycosidesetc.M.oleiferaflowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity.The anti-inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium.Conclusions:The results of our study suggest that flowers ofM.oleiferapossess potent anti-inflammatory activity and are also a good source of natural antioxidants.Further study is needed to identify the chemical compounds responsible for their anti-inflammatory activity.

Quantification of total phenol,flavonoid content and pharmacognostical evaluation including HPTLC fingerprinting for the standardization of Piper nigrum Linn fruits

Objective:To carry out the physicochemical and phytochemical standardization with high performance thin layer chromatography fingerprinting of Piper nigrum L.(P.nigrum)fruits in order to ascertain the standard pharmacognostical parameters of this king of spices.Methods:Many standardization parameters like extractive values,total ash value,water soluble ash value and acid insoluble ash,moisture content,loss on drying and pH values of P.nigrum L.fruits were analyzed.The method of Harborne was adopted for the preliminary phytochemicals screening.Analysis of total phenolic and flavonoid contents,pesticides residues,aflatoxin and heavy metals were also performed.CAMAG-high performance thin layer chromatography system was used for fingerprinting of methanolic extract of P.nigrum L.fruits.Results:The results of phytochemicals testing indicated the presence of carbohydrates,phenolic compounds,flavonoids,alkaloids,proteins,saponins,lipids,sterols and tannins in various solvent extracts.Total phenolic and flavonoid contents in methanolic extract were found to be 1.728 1 mg/g and 1.087 ug/g,respectively.Heavy metals concentrations were found to be within standard limits.Aflatoxins and pesticides residues were absent.Conclusions:The outcome of this study might prove beneficial in herbal industries for identification,purification and standardization of P.nigrum L.fruits.

GC-MS analysis,determination of total phenolics,flavonoid content and free radical scavenging activities of various crude extracts of Moringa peregrina(Forssk.) Fiori leaves

Objective:To perform phytochemical screening,estimate total phenolics,flavonoids and to evaluate antioxidant potential of Moringa peregrina(M.peregrina) leaves.Methods:The dried powdered leaves of M.peregrina(150 g) were extracted exhaustively by Soxhlet with ethanol and then fractionated into hexane,chloroform,ethy alacetate and methanol.All the prepared extracts were also analyzed by gas chromatography-mass spectrometry to identify and characterize the chemical compounds present in the crude extracts.Folin- Ciocalteu reagent and aluminium chloride colorimetric methods were used to estimate total phenolic and flavonoid content of extracts.Hydrogen peroxide and 1,1 diphenyl-2-picrylhydrazyl were used to determine in vitro antioxidant activity.Results:Phytochemical analysis of ethanol extract showed presence of major classes of phytochemicals.Gas chromatography-mass spectrometry results revealed presence of 19 phytoconstituents in hexane extract,6 in ethyl acetate and 7 compounds in methanolic extract.Methanol extract was found to contain the highest phenolic content and flavonoids.In vitro antioxidant activities of all crude extracts were significant and comparable with the standard ascorbic acid.Conclusions:Results of this study show that the leaves of M.peregrina are the rich source of phenolic compounds that can play an important role in preventing the progression of many diseases.

Phytochemistry and potential therapeutic actions of Boswellic acids:A mini-review

The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids(BA).The oleo gum resin obtained from Indian variety i.e.Boswellia serrata(Family – Burseraceae) is commonly known as Salai guggal.The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono,di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars.This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory,anti-arthritic,antirheumatic,anti-diarrheal,anti-hyperlipidemic,anti-asthmatic,anti-cancer,anti-microbial anti-fungal,anti-complementary and analgesic activity,etc.It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases.Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel,potent,specific antiinflammatory agents due to non-redox inhibition of 5-lipoxygenase(5-LO) enzyme.However,the other important targets of Boswellic acids also include topoisomerases,angiogenesis,and cytochrome p450 enzymes.This review is a sincere attempt to discuss and present the current status of therapeutic potential,phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B.serrata.

COVID-19-associated mucormycosis and treatments

In the current pandemic,COVID-19 patients with predisposing factors are at an increased risk of mucormycosis,an uncommon angioinvasive infection that is caused by fungi with Mucor genus which is mainly found in plants and soil.Mucormycosis development in COVID-19 patient is related to various factors,such as diabetes,immunocompromise and neutropenia.Excessive use of glucocorticoids for the treatment of critically ill COVID-19 patients also leads to opportunistic infections,such as pulmonary aspergillosis.COVID-19 patients with mucormycosis have a very high mortality rate.This review describes the pathogenesis and various treatment approaches for mucormycosis in COVID-19 patients,including medicinal plants,conventional therapies,adjunct and combination therapies.

Unusual presentation of Erdheim-Chester disease in a child with acute lymphoblastic leukemia

Erdheim-Chester disease(ECD) is an uncommon, nonfamilial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic features include bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal parts of the long bones, or bilateral symmetrically abnormal intense 99 mTechnetium labelling of the metaphyseal-diaphyseal region of the long bones, and computed tomography scan findings of "coated aorta" or "hairy kidneys". ECD in childhood with osteolytic lesion is extremely rare. We describe an unusual case with an expansile lytic bone lesion at presentation in a case of acute lymphoblastic leukemia.

Preoperative embolization of primary bone tumors:A case control study

AIM:To study the safety and effectiveness of preoperative embolization of primary bone tumors in relation to intraoperative blood loss,intraoperative blood transfusion volume and surgical time.METHODS:Thirty-three patients underwent preoperative embolization of primary tumors of extremities,hip or vertebrae before resection and stabilization.The primary osseous tumors included giant cell tumors,aneurysmal bone cyst,osteoblastoma,chondroblastoma and chondrosarcoma.Twenty-six patients were included for the statistical analysis(embolization group)as they were operated within 0-48 h within preoperative embolization.A control group(non-embolization group,n = 28)with bone tumor having similar histological diagnosis and operated without embolization was retrieved from hospital record for statistical comparison.RESULTS:The mean intraoperative blood loss was 1300 mL(250-2900 mL),the mean intraoperative blood transfusion was 700 m L(0-1400 m L)and the mean surgical time was 221 ± 76.7 min for embolization group(group Ⅰ,n = 26).Non-embolization group(group Ⅱ,n = 28),the mean intraoperative blood loss was 1800 m L(800-6000 m L),the mean intraoperative blood transfusion was 1400 mL(700-8400 mL)and the meansurgical time was 250 ± 69.7 min.On comparison,statistically significant(P < 0.001)difference was found between embolisation group and non-embolisation group for the amount of blood loss and requirement of blood transfusion.There was no statistical difference between the two groups for the surgical time.No patients developed any angiography or embolization related complications.CONCLUSION:Preoperative embolization of bone tumors is a safe and effective adjunct to the surgical management of primary bone tumors that leads to reduction in intraoperative blood loss and blood transfusion volume.

In vitro inhibitory effects on a-glucosidase and a-amylase level and antioxidant potential of seeds of Phoenix dactylifera L.

Objective:To evaluate and compare the antioxidant activity,total phenolic contents(TPCs) and in vitro antidiabetic activity of various pits extracts obtained from five Omani date cultivars.Methods:Sun-dried mature fruits of five Omani date varieties,namely,Fardh,Naghal,Khalas,Khinazi and Khasab were purchased from the local market in Muscat,Oman in the month of September 2014.Four seed extracts viz.water,ethanol,methanol and acetone were prepared for each date variety and their antioxidant activities were investigated by 1,1-diphenyl-2-picrylhydrazyl,hydrogen peroxide scavenging method and reducing power assay method,respectively.In vitro antidiabetic activity of the date pit extracts was evaluated by measuring their inhibitory effect on a-glucosidase and aamylase level.TPCs were also quantified colorimetrically.Results:The results indicated that TPC of date seeds was solvent dependent.Acetone,ethanol and methanol were found to be significantly better solvents than water in extracting phenolic compounds from the date seeds.Pit extracts exhibited moderate to good in vitro antioxidant activity and increased reducing power.Among all date pit extracts,water extract exhibited significant in vitro antidiabetic activity in comparison to standard drug,acarbose.Conclusions:The present study confirms that disposed waste of Omani dates is a rich source of dietary antioxidant because of its high TPC.The pits due to their inhibitory effects on a-glucosidase and a-amylase level could be used as a monotherapy along with an appropriate diabetic diet and exercise or might be in conjunction with antidiabetic therapy to manage and prevent progression of diabetes.

Eslicarbazepine acetate:A therapeutic agent of paramount importance in acute anticonvulsant therapy

Eslicarbazepine acetate (ESL) is a new, once daily, orally administered, third generation antiepileptic drug which is indicated in the treatment of partial-onset seizures. ESL is known to exert it's anticonvulsant effect by blocking the voltage-gated sodium channels. Several clinical trials and pharmacological studies have revealed that seizure control was better with ESL monotherapy (1 200 or 1 600 mg once daily) following a switch from other antiepileptic drugs in comparison with pseudo-placebo patients. The studies have indicated the ESL to be well tolerated and produced only mild to moderate emergent adverse events with the therapy. Being a dibenzazepine family member, structure and chemistry of ESL resembles more or less to carbamazepine and oxcarbazepine. ESL differs structurally from carbamazepine and oxcarbazepine at the 10, 11 position of dibenazepine nucleus. This molecular variation results in differences in metabolism and thus helps to prevent the formation of toxic epoxide metabolites. ESL following oral administration is rapidly metabolised to active metabolite namely S-licarbazepine which is responsible for its pharmacological activity. ESL exhibits acceptable pharmacokinetic profile and shows insignificant drug-drug interactions. In phase III clinical program, ESL was found to be efficacious and well tolerated in adult patients with partial onset seizures previously not controlled with treatment with one or two other antiepileptic drugs.

Role of locking plates in treatment of difficult ununited fractures： a clinical study

Objective： To present our experience in treatment of difficult ununited long bone fractures with locking plate. Methods： Retrospective evaluation of locking plate fixation in 10 difficult nonunions of long bone fractures was done. Fixation was done with locking plate for femoral shaft fracture （3 patients）, supracondylar fracture of femur （gap nonunion）, fracture of clavicle, fracture of both forearm bones （radius and ulna） fracture of ulna, fracture of shaft of humerus, fracture of tibial diaphysis and supracondylar frac- ture of humerus （one patient each）. Five fractures had more than one previous failed internal fixation. One patient had infected nonunion which was managed by debridement with cast immobilization followed by fixation with locking plate at six weeks. Seven fractures were atrophic, two were oligotrophic, and one was hypertrophic. Fibular autograft was used in 2 cases and iliac crest cancellous bone graft used in all the patients. Results： Minimum follow-up was 6 months （range, 6 months to 2.5 years）. Average time for union was 3.4 months （range 2.5 to 6 months）. None of the patients had plate- related complications or postoperative wound infections. Conclusion： Along with achieving stability with locking compression plate, meticulous soft tissue dissection, acceptable reduction, good fixation technique and bone grafting can help achieve union in difficult nonunion cases. Though locking plate does not by itself ensure bony union, we have found it to be another useful addition to our armamentarium for treating difficult fracture nonunions.

Spontaneous atraumatic dislocation of sternoclavicu- lar joint in Reiter＇s syndrome

Reactive arthritis or Reiter＇s syndrome characteristically affects the joint of the lower limb in an asymmetrical pattern. Usually it does not affect the axial skeleton or upper limbs. Although cases of atraumatic at- lantoaxial subluxations have been reported, no case of spon- taneous sternoclavicular dislocation in Reiter＇s syndrome has been reported. This paper describes a case of a 26 year old male patient who developed a spontaneous posterior sternoclavicular joint dislocation. No attempt of reduction was made and the patient was managed conservatively with good results.

Ethnobotany,phytochemistry and pharmacological potential of Vitex negundo L.(five-leaved chaste tree):An updated review

In the past two decades,a shift in paradigm has been observed in the development of new drugs from the plants for the treatment of diseases.Many scientists are focusing on the evidence based use of medicinal plants to develop pharmacotherapy for various human ailments.An important medicinal plant that has caught the attention of researchers all over the globe is Vitex negundo Linn.This plant is commonly used in various traditional systems of medicine like Ayurveda,Chinese,Siddha and Unani to treat various diseases and has been the subject of extensive research studies lately.Its roots and leaves are widely used in various disorders and illnesses such as skin eczema,ringworm,liver disorders,spleen enlargement,rheumatic pain,gout,abscess,backache etc.Seeds are also used as folklore medicine in bronchitis,eye disorders,female reproductive disorders,cold,dropsy,malarial fever and as demulcent.The current article is an effort to compile an updated review to disseminate knowledge and information among the scientific fraternity covering the progress made in the pharmacology and phytochemistry of this useful medicinal plant.This review on a very important traditional medicine,Vitex negundo L.can serve as a reference to the scientific community for their future research on this plant.

Chemical modification of acetaminophen：PASS assisted in vivo antiinflammatory activity of chalcones,flavanones and Schiff bases

In the present study,synthetic chalcones,flavanones and Schiff bases were prepared starting from paraceamol,and evaluated their anticipated anti-inflammatory activity.Chalcones were synthesized by reacting 3-acetyl-4-hydroxy acetanilide and aromatic aldehydes in alcoholic potassium hydroxide(KOH) solution under Claisen-Schmidt condensation conditions.The chalcones were cyclized in the presence of piperidine in isoamyl alcohol to obtain flavonone derivatives.Schiff bases were synthesized by condensing 3-acetyl-4-hydroxy anilines with aromatic aldehydes in the presence of HCl.These Schiff bases were further reacted with other aromatic aldehydes in alcoholic KOH solution.PASS cheminformatics software was used to predict the anti-inflammatory activity of synthesized compounds.PASS software predicted that chalcone-based Schiff bases 6a–d contained structural features that can exhibit anti-inflammatory activity.All the prepared derivatives of acetaminophen exhibited moderate to excellent in vivo anti-inflammatory activity in carrageenan-induced edema in rat paw.All the Schiff bases coupled chalcones showed good anti-inflammatory activity compared with the reference drug,diclofenac.Further evaluation of their therapeutic potential and safety profile is required in the future study.

Evaluation of antioxidant potential,total phenolic content and phytochemical screening of aerial parts of a folkloric medicine,Haplophyllum tuberculatum(Forssk)A.Juss

Objective:To quantify total phenols,flavonoids and to investigate the in vitro antioxidant power of Haplophyllum tuberculatum(H.tuberculatum)leaves extracts of varying polarities.Methods:The authenticated sample of H.tuberculatum(50 g)leaves was dried under shade,powdered and extracted exhaustively with ethanol by cold percolation method.The alcoholic extract was further partitioned into petroleum ether,acetone,chloroform and methanol to obtain the fractions of varying polarities which were subjected to qualitative phytochemical testing.Total phenolics and flavonoids content in the acetone,chloroform and methanol extracts were quantified by using standard colorimetric methods.Petroleum ether extract was omitted because it did not show the presence of either tannins or flavonoids.In vitro antioxidant activity and total antioxidant capacity were determined by using 1,1 diphenyl-2-picrylhydrazyl radical and phosphomolybdenum reagent.Ascorbic acid was used as a reference antioxidant for comparison purpose.Results:Qualitative phytochemical results of leaves extracts confirmed the presence of major secondary plant metabolites.The extraction of phenolic compounds varied considerably according to the polarity of solvent.The most polar fractions i.e.methanol were observed to have the highest phenolic content(561.22 mg/g of gallic acid equivalent)and flavonoids(165.54 mg/g of quercetin equivalent).Although the free radical scavenging activity of leaves fractions was noted to be slightly lower than the reference compound,a direct relationship was observed between phenolic content and in vitro antioxidant activity.On the other hand,leaves fractions exhibited significant total antioxidant capacity as ascorbic acid equivalent.Conclusions:The aerial part of H.tuberculatum is rich in phenolic compounds which might play a vital role in the discovery of natural antioxidants.