Macrophage Repolarization as a Therapeutic Strategy for Osteosarcoma.

Macrophages are versatile immune cells and can adapt to both external stimuli and their surrounding environment. Macrophages are categorized into two major categories; M1 macrophages release pro-inflammatory cytokines and produce protective responses that lead to antimicrobial or antitumor activity. M2 or tumor-associated macrophages (TAM) release anti-inflammatory cytokines that support tumor growth, invasion capacity, and metastatic potential.

Human macrophage-engineered vesicles for utilization in ovarian cancer treatment.

Background: Ovarian cancer is a deadly female malignancy with a high rate of recurrent and chemotherapy-resistant disease. Tumor-associated macrophages (TAMs) are a significant component of the tumor microenvironment and include high levels of M2-protumor macrophages that promote chemoresistance and metastatic spread. M2 macrophages can be converted to M1 anti-tumor macrophages, representing a novel therapeutic approach.

Dendritic Cell Membrane-Derived Nanovesicles for Targeted T Cell Activation.

T cells play an integral role in the generation of an effective immune response and are responsible for clearing foreign microbes that have bypassed innate immune system defenses and possess cognate antigens. The immune response can be directed toward a desired target through the selective priming and activation of T cells. Due to their ability to activate a T cell response, dendritic cells and endogenous vesicles from dendritic cells are being developed for cancer immunotherapy treatment.

Protein sequence design with a learned potential.

The task of protein sequence design is central to nearly all rational protein engineering problems, and enormous effort has gone into the development of energy functions to guide design. Here, we investigate the capability of a deep neural network model to automate design of sequences onto protein backbones, having learned directly from crystal structure data and without any human-specified priors. The model generalizes to native topologies not seen during training, producing experimentally stable designs.

Deficiency in indoleamine-2, 3-dioxygenase induces upregulation of guanylate binding protein 1 and inducible nitric oxide synthase expression in the brain during cerebral infection with Toxoplasma gondii in genetically resistant BALB/c mice but not in genetically susceptible C57BL/6 mice.

We examined the roles of indoleamine-2, 3-dioxygenase 1 (IDO1) in controlling cerebral Toxoplasma gondii infection in both genetically resistant and susceptible strains of mice. In susceptible C57BL/6 mice, IDO expression was immunohistochemically detected only in a minority (22.5%) of tachyzoite-infected cells in their brains during the later stage of infection.

Optical control of fast and processive engineered myosins in vitro and in living cells.

Precision tools for spatiotemporal control of cytoskeletal motor function are needed to dissect fundamental biological processes ranging from intracellular transport to cell migration and division. Direct optical control of motor speed and direction is one promising approach, but it remains a challenge to engineer controllable motors with desirable properties such as the speed and processivity required for transport applications in living cells. Here, we develop engineered myosin motors that combine large optical modulation depths with high velocities, and create processive myosin motors with optically controllable directionality.

Evaluation of In vitro and In vivo Protective Efficacy of Bauhinia variegata Against Leishmania donovani in Murine Model.

Purpose: Visceral leishmaniasis is one of the ignored parasitic infection affecting millions of people globally. Currently, available treatment options are unsatisfactory because of high cost and side effects of the leishmanicidal drugs. Therefore, herbal medicines provide a promising choice for the detection of efficient and novel leishmanicidal therapeutics which can rejuvenate the immune response of the host with less adverse effects.

Conjugation reaction with ferulic acid boosts the antioxidant property of arabinogalactan-protein and enhances its ability to form complex with β-lactoglobulin.

Ferulic acid was chemically grafted onto the arabinogalactan protein of Aegle marmelos fruit gum using 1,1'-carbonyldiimidazole as coupling reagent. Thus, grafted polysaccharides with different degrees of substitution were prepared and then characterized by gas chromatography/mass spectrometry, size exclusion chromatography, and ultraviolet-visible, infra-red, and nuclear magnetic resonance spectroscopic investigations. Fluorescence spectroscopic investigation showed hydrophobic microdomain formation in grafted polymers.

Pathologic Hip Fracture by Virtue of a Rare Osseous Manifestation of Gout: A Case Report.

Case: A 76-year-old woman without a personal or family history of gout presented with complaints of left hip pain after a mechanical fall from her wheelchair. Advanced imaging revealed a nonspecific lesion and nondisplaced fracture of the femoral neck. Intraoperative biopsy from the lesion/fracture demonstrated tophaceous gout.

Chemically sulfated polysaccharides from natural sources: Assessment of extraction-sulfation efficiencies, structural features and antiviral activities.

The provisioning of compound libraries with a high degree of diversity and attractive pharmacological properties is a limiting step in drug development. This study reports the production of highly bioactive sulfated polysaccharides, originally present in a nonsulfated, dormant state in natural sources, and demonstrates their antiviral activity (human cytomegalovirus EC values of 2.34-7.

Chemical profile of a polysaccharide from Psidium guajava leaves and it's in vivo antitussive activity.

Decoction of Psidium guajava leaves has been used as medication for chronic coughs and breathlessness for ages. Despite demonstration of antitussive activity, the specific molecule responsible for this remains unidentified. Herein, we report chemical profile and antitussive activity of its water extract (WE) and a polysaccharide (F1) present therein.

Antiparasitic and immunomodulatory potential of oral nanocapsules encapsulated lactoferrin protein against Plasmodium berghei.

Aim: To analyze the effect of native buffalo lactoferrin (buLf) protein along with its nanoformulation using alginate-enclosed, chitosan-conjugated, calcium phosphate buffalo Lf nanocapsules (AEC-CCo-CP-buLf NCs) against rodent parasite Plasmodium berghei.

Materials & Methods: BALB/c mice were infected with malaria parasite and efficacy of the proteins (buLf and NCs) was evaluated by measuring parasitemia, initialization, role of miRNA in absorption of NCs, parasite load by histopathology and quantitative determination, cytokine levels, bioavailability and immunohistochemistry to localize Lf protein.

Results: NCs significantly reduced the parasite load in mice compared with buLf and untreated group.

Oral administration of encapsulated bovine lactoferrin protein nanocapsules against intracellular parasite Toxoplasma gondii.

Toxoplasma gondii is a deadly intracellular parasite known to reside in every nucleated cell and known to cause severe complications in immunocompromised host. Standard drugs are cost effective and cause side effects, therefore, there is a necessity for a new drug molecule with immunomodulatory potential. Lactoferrin (Lf) is a natural milk protein, which has shown antimicrobial properties in its nanoformulation using alginate chitosan calcium phosphate bovine lactoferrin nanocapsules (AEC-CCo-CP-bLf-NCs).

Metal-free aerobic one-pot synthesis of substituted/annulated quinolines from alcohols via indirect Friedländer annulation.

Metal-free, operationally simple, and highly efficient one-pot aerobic process for the synthesis of functionalized/annulated quinolines is devised from easily available 2-aminobenzyl alcohol/2-aminobenzophenones and alkyl/aryl alcohols for the first time. The process involves two sequential reactions, namely in situ aerial oxidation of alcohols to the corresponding aldehydes/ketones followed by Friedländer annulation.

Effect of lactoferrin protein on red blood cells and macrophages: mechanism of parasite-host interaction.

Background: Lactoferrin is a natural multifunctional protein known to have antitumor, antimicrobial, and anti-inflammatory activity. Apart from its antimicrobial effects, lactoferrin is known to boost the immune response by enhancing antioxidants. Lactoferrin exists in various forms depending on its iron saturation.

Regioselective synthesis of dihydrothiophene and thiopyran frameworks via catalyst-controlled intramolecular Cγ/Cδ-S fusion of α-allyl-β'-oxodithioesters.

A highly efficient and atom-economic dual reaction manifold has been developed to synthesize 4H-thiopyran and 4,5-dihydrothiophene frameworks via regioselective intramolecular C-S fusion of α-allyl-β'-oxodithioesters. The ring size of the sulfur-heterocycles has been efficiently tuned by the use of two different catalytic systems. Palladium activates the Cδ-H of the allyl termini and facilitates the intramolecular Cδ-S coupling to furnish six-membered thiopyran skeletons exclusively.

Lewis acid promoted construction of chromen-4-one and isoflavone scaffolds via regio- and chemoselective domino Friedel-Crafts acylation/Allan-Robinson reaction.

A facile and efficient synthesis of chromen-4-one and isoflavone frameworks is achieved by the domino C-acylation/O-acylation/aldolization sequence. This operationally simple one-pot elegant strategy provides structurally unique chromen-4-ones and isoflavones directly from phenols via concomitant formation of multiple C-C and C-O bonds in a single operation. The outcomes of the buttressing effect, substituent dependence, and catalyst and solvent specificity during the course of the Friedel-Crafts acylation reactions are demonstrated and supported by fitting experiments.

Identification of 1-[4-Benzyloxyphenyl)-but-3-enyl]-1H-azoles as New Class of Antitubercular and Antimicrobial Agents.

A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1H-azoles has been identified as potent antitubercular agents against Mycobacterium tuberculosis. Synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. Several of the compounds 26, 34, and 36 exhibited significant antitubercular activities with MIC value as low as 1.

A strategy for the synthesis of anthraquinone-based aryl-C-glycosides.

An efficient and simple strategy for the synthesis of a diverse range of anthraquinone-based aryl-C-glycosides has been developed. It involves the sequential Diels-Alder reaction and oxidative aromatization with the preformed glycosyl diene and dienophiles. The glycosyl dienes were obtained from simple sugars by tandem one-pot substitution and elimination reaction.

Synthesis and evaluation of small libraries of triazolylmethoxy chalcones, flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG.

A synthetic strategy to access small libraries of triazolylmethoxy chalcones 4{1-20}, triazolylmethoxy flavanones 5{1-10} and triazolylmethoxy aminopyrimidines 6{1-17} from a common substrate 4-propargyloxy-2-hydroxy acetophenone using a set of different reactions has been developed. The chalcones and flavanones were screened against mycobacterial FAS-II pathway using a recombinant mycobacterial strain, against which the most potent compound showed ∼88% inhibition in bacterial growth and substantially induction of reporter gene activity at 100 μM concentration. The triazolylmethoxy aminopyrimdines were screened against PknG of Mycobaceterium tuberculosis displaying moderate to good activity (23-53% inhibition at 100 μM), comparable to the action of a standard inhibitor.

Microarray in parasitic infections.

Modern biology and genomic sciences are rooted in parasitic disease research. Genome sequencing efforts have provided a wealth of new biological information that promises to have a major impact on our understanding of parasites. Microarrays provide one of the major high-throughput platforms by which this information can be exploited in the laboratory.

Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2-aminopyrimidines as antitubercular and antidiabetic agents.

An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H(37)Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.

Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones as novel antioxidants and antihyperlipidemics.

An economical and efficient one-pot synthesis of a series of novel 5-aryl-6-cinnamoyl-7-methyl-flavanones has been developed by simple refluxing of cinnamoyl chalcones with NaOAc in aqueous ethanol in quantitative yields. These flavanones were screened for their in vitro antioxidant and in vivo antidyslipidemic activities. Among 24 compounds screened, four compounds 28, 29, 30, and 48 showed significant antidyslipidemic activities.

Synthesis and optimization of antitubercular activities in a series of 4-(aryloxy)phenyl cyclopropyl methanols.

A series of [4-(aryloxy)phenyl]cyclopropyl methanones were synthesized by reaction of different benzyl alcohols with 4-chloro-4'-fluorobutyrophenone in DMF in the presence of NaH/TBAB. The methanones were further reduced to respective methanols. The antitubercular activity of these compounds was evaluated in vitro against Mycobacterium tuberculosis H37Rv.