Molecular Interactions Between Innate and Adaptive Immune Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications

Innate immunity constitutes the first line of host defense against various anomalies in humans, and it also guides the adaptive immune response. The function of innate immune components and adaptive immune components are interlinked in hematological malignancies including chronic lymphocytic leukemia (CLL), and molecular interactions between innate and adaptive immune components are crucial for the development, progression and the therapeutic outcome of CLL. In this leukemia, genetic mutations in B cells and B cell receptors (BCR) are key driving factors along with evasion of cytotoxic T lymphocytes and promotion of regulatory T cells. Similarly, the release of various cytokines from CLL cells triggers the protumor phenotype in macrophages that further edges the CLL cells. Moreover, under the influence of various cytokines, dendritic cells are unable to mature and trigger T cell mediated antitumor response. The phenotypes of these cells are ultimately controlled by respective signaling pathways, the most notables are BCR, Wnt, Notch, and NF-κB, and their activation affects the cytokine profile that controls the pathogenesis of CLL, and challenge its treatment. There are several novel substances for CLL under clinical development, including kinase inhibitors, antibodies, and immune-modulators that offer new hopes. DC-based vaccines and CAR T cell therapy are promising tools; however, further studies are required to precisely dissect the molecular interactions among various molecular entities. In this review, we systematically discuss the involvement, common targets and therapeutic interventions of various cells for the better understanding and therapy of CLL

Size selectivity in antibiofilm activity of 3-(Diphenylphosphino)propanoic acid coated gold nanomaterials against Gram positive Staphylococcus aureus and Streptococcus mutans

Abstract Biofilm formation by pathogenic bacteria is one of the major threats in hospital related infections, hence inhibiting and eradicating biofilms has become a primary target for developing new anti-infection approaches. The present study was aimed to develop novel antibiofilm agents against two Gram-positive bacteria; Staphylococcus aureus (ATCC 43300) and Streptococcus mutans (ATCC 25175) using gold nanomaterials conjugated with 3-(diphenylphosphino)propionic acid (Au-LPa). Gold nanomaterials with different sizes as 2–3 nm small and 9–90 nm (50 nm average size) large were stabilized by LPa via different chemical synthetic strategies. The nanomaterials were fully characterized using atomic force microscope (AFM), transmission electron microscope, ultraviolet–visible absorption spectroscopy, and Fourier transformation infrared spectroscopy. Antibiofilm activity of Au-LPa nanomaterials was tested using LPa alone, Au-LPa and unprotected gold nanomaterials against the both biofilm-producing bacteria. The results showed that LPa alone did not inhibit biofilm formation to a significant extent below 0.025 mM, while conjugation with gold nanomaterials displayed manifold enhanced antibiofilm potential against both strains. Moreover, it was also observed that the antibiofilm potency of the Au-LPa nanomaterials varies with size variations of nanomaterials. AFM analysis of biofilms further complemented the assay results and provided morphological aspects of the antibiofilm action of Au-LPa nanomaterials

Gold nanoparticle conjugation enhances the antiacanthamoebic effects of chlorhexidine

Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was con- firmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a goldconjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 M. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth assays. In contrast, chlorhexidine alone, at a similar concentration, showed limited effects. Notably, neomycin alone or conjugated with nanoparticles did not show amoebicidal or amoebistatic effects. Pretreatment of A. castellanii with goldconjugated chlorhexidine nanoparticles reduced amoeba-mediated host cell cytotoxicity from 90% to 40% at 5 M. In contrast, chlorhexidine alone, at similar concentrations, had no protective effects for the host cells. Similarly, amoebae treated with neomycin alone or neomycin-conjugated nanoparticles showed no protective effects. Overall, these findings suggest that gold-conjugated chlorhexidine nanoparticles hold promise in the improved treatment of A. castellanii keratitis

1,1-Diphenyl-2-picrylhydrazyl radical scavenging activity of novel dihydropyridine derivatives

Thirteen dihydropyridine analogues 1-13 were synthesized and evaluated for their DPPH radical scavenging activity. A good to moderate antioxidant activity ranging from 127.4 to 284.5 μM was observed and structure-activity relationship was established. The 3'-fluoro derivative 8 (IC50 = 127.4±3.5 μM) was found to exhibit highest activity among the dihydro pyridine derivatives 1-13, while the other derivatives 11 (IC50 = 132.5±3.32 μM), 6 (IC50 = 142.2±0.60 μM), 10 (IC50 = 144.7±2.46 μM), 12 (IC50 = 153.7±0.50 μM), 5 (IC50 = 161.4±2.81 μM) and 5 (IC50 = 164.4±2.50 μM) possess moderate activity, depends upon the C-4 and C-6 substituted groups. The compounds 7, 13, 4, 3 and 2 have lowest IC50 values, ranging between 172.8 and 284.5 μM. Dihydropyridine analogues were characterized by spectroscopic techniques

Digestive cellulose hydrolyzing enzyme activity (endo- β–1, 4- D-glucanase) in the gut and salivary glands of blister beetle, Mylabris pustulata

Abstract.-Mylabris pustulata (blister beetle) was studied for the enzymes involved in hydrolysis of cellulose. Carboxy methyl cellulose hydrolyzing activity (endo-β-1, 4-D-glucanase) was detected in the salivary glands and fore gut, very little activity was present in the hind gut. The multiple forms of the enzyme activity were detected on zymogram after non-denaturing PAGE. One of the fractions was purified by gel filtration and preparative native PAGE. The purified protein appeared as single band on SDS-PAGE with a molecular weight of 150 kilo Dalton. The characteristics of the enzyme showed two optimum pH values, one acidic and one neutral 2.0 and 7. The optimum temperature for endo-β -D-1, 4-glucanase was 50 °C. The enzyme was maximum activity against carboxy methyl cellulose. Km and Vmax of the enzyme was determined as 0.6g/l and 0.3, respectively. To our knowledge this is first report on the digestive cellulose hydrolyzing activity of Mylabris pustulata

Staphylococcus arlettae mediated defense mechanisms and metabolite modulation against arsenic stress in Helianthus annuus

IntroductionArsenate, a metalloid, acting as an analog to phosphate, has a tendency to accumulate more readily in plant species, leading to adverse effects.MethodsIn the current study, sunflower seedlings were exposed to 25, 50 and 100 ppm of the arsenic.ResultsLikewise, a notable reduction (p<0.05) was observed in the relative growth rate (RGR) by 4-folds and net assimilation rate (NAR) by 75% of Helianthus annuus when subjected to arsenic (As) stress. Nevertheless, the presence of Staphylococcus arlettae, a plant growth-promoting rhizobacterium with As tolerance, yielded an escalation in the growth of H. annuus within As-contaminated media. S. arlettae facilitated the conversion of As into a form accessible to plants, thereby, increasing its uptake and subsequent accumulation in plant tissues. S. arlettae encouraged the enzymatic antioxidant systems (Superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX) and catalase (CAT)) and non-enzymatic antioxidants (flavonoids, phenolics, and glutathione) in H. annuus seedlings following substantial As accumulation. The strain also induced the host plant to produce osmolytes like proline and sugars, mitigating water loss and maintaining cellular osmotic balance under As-induced stress. S. arlettae rectified imbalances in lignin content, reduced high malonaldehyde (MDA) levels, and minimized electrolyte leakage, thus counteracting the toxic impacts of the metal.ConclusionThe strain exhibited the capability to concurrently encourage plant growth and remediate Ascontaminated growth media through 2-folds rate of biotransformation and bio-mobilization

PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study

Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV-or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was "reuse of syringes" while in triple infection it was "intravenous drug users" (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration

Application of algal nanotechnology for leather wastewater treatment and heavy metal removal efficiency

Wastewater from tanneries may ruin agricultural fields by polluting them with trace metals. The synthesis of nanoparticles (NPs) from algal sources and their application could help in decreasing hazardous materials, for environmental safety. The potential of zinc oxide nanoparticles made from Oedogonium sp. was evaluated for removal of heavy metals from leather industrial wastewater. Synthesized algal nanoparticles (0 (control), 0.1, 0.5, and 1 mg) were applied to treat wastewater by using different concentrations of leather industrial effluents (0%, 5%, 10%, 15%, and 100%) for 15, 30, and 45 d. The wastewater collected was dark brown to black in color with very high pH (8.21), EC (23.08 μs/cm), and TDS, (11.54 mg/L), while the chloride content was 6750 mg/L. The values of biological oxygen demand (BOD) and chemical oxygen demand (COD) ranged between 420 mg/L and 1123 mg/L in the current study. Prior to the application of nanoparticles, Cr (310.1), Cd (210.5), and Pb (75.5 mg/L) contents were higher in the leather effluents. The removal efficiency of TDS, chlorides, Cr, Cd, and Pb was improved by 46.5%, 43.5%, 54%, 57.6%, and 59.3%, respectively, following treatment with 1 mg of nanoparticles after 45 d. Our results suggested that the green synthesis of ZnO nanoparticles is a useful and ecofriendly biotechnological tool for treating tannery effluents, before they are discharged into water bodies, thus making the soil environment clean.Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia | Ref. PNURSP2022R7