Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus.

In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer's results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes.

Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations.

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein-ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein-ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between -1.11 to 1.48 and -1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of -38.88 to -31.32 and -31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein-ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression.

Corrigendum to "Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations" [Saudi Pharm. J. 31(6) (2023) 1061-1067].

[This corrects the article DOI: 10.1016/j.jsps.2023.05.002.].

Treatment of Chronic Hematogenous Osteomyelitis in Children With Antibiotic Impregnated Calcium Sulphate.

BACKGROUND: The purpose of this study was to evaluate the clinical and radiologic outcome of chronic hematogenous osteomyelitis (CHOM) in children, treated with single-stage debridement and dead space management using antibiotic impregnated calcium sulphate pellets. METHODS: The authors retrospectively evaluated a consecutive series of 34 patients who presented with CHOM from 2011 to 2017. In each case, CHOM was classified according to the Beit CURE classification. Following thorough surgical debridement, the resulting dead space in the bone was filled with the antibiotic impregnated beads before primary closure. RESULTS: Of the 31 patients available for follow up, effective regeneration of bone was confirmed in all cases, with radiographic bone healing typically observed at around 12 weeks. None of the children required reoperation for infection and none had recurrence of infection at the time of final review. The beads were completely absorbed within 3 months. No systemic adverse reactions to the local delivery of antibiotics were observed in this study. CONCLUSIONS: The authors found that single-stage debridement in conjunction with antibiotic impregnated calcium sulphate was an effective means of treating CHOM in children, with effective eradication of infection in every case. LEVEL OF EVIDENCE: Level IV-Retrospective case series. See instructions for authors for a complete description of levels of evidence.

Rejection of the beneficial acclimation hypothesis (BAH) for short term heat acclimation in Drosophila nepalensis.

Beneficial acclimation hypothesis (BAH) is the phenotypic plasticity in response to changing environments which enables organisms to enhance their fitness. In recent years, however, BAH has received vigorous criticism and is still debatable. In this study, we tested thermal hardiness phenotypes (melanization, chill coma recovery, heat knockdown and percentage survival) on adult and pre-adult stages of Drosophila nepalensis, reared in different thermal environments (14, 17, 21 and 25 °C) to check whether increasing natural surrounding temperature and acclimation limit towards environmental change is detrimental or beneficial. Results showed that rearing D. nepalensis at higher temperatures (21 and 25 °C) reduces its melanization and cold hardiness but improves heat knockdown times. When temperature was raised to 26.2 °C (0.6 °C above the upper thermal maxima), to determine the short-term acclimation effects, survival and fitness of adults diminished approximately 1.5 to 2 folds. These results suggest that D. nepalensis has long-term developmental acclimation to both heat and cold which would be extremely beneficial as temperatures and climates alter in the region due to global warming. However, a lack of short-term heat acclimation suggests that rapid shifts in thermal extreme could be detrimental to D. nepalensis.

Effect of basic oxygen furnace slag particle size on sequestration of carbon dioxide from landfill gas.

The mineral carbon sequestration capacity of basic oxygen furnace (BOF) slag offers great potential to absorb carbon dioxide (CO2) from landfill emissions. The BOF slag is highly alkaline and rich in calcium (Ca) containing minerals that can react with the CO2 to form stable carbonates. This property of BOF slag makes it appealing for use in CO2 sequestration from landfill gas. In a previous study, CO2 and CH4 removal from the landfill gas was investigated by performing batch and column experiments with BOF slag under different moisture and synthetic landfill gas exposure conditions. The study showed two stage CO2 removal mechanism: (1) initial rapid CO2 removal, which was attributed to the carbonation of free lime (CaO) and portlandite [(Ca(OH)2)], and (2) long-term relatively slower CO2 removal, which was attributed to be the gradual leaching of Ca2+ from minerals (calcium-silicates) present in the BOF slag. Realising that the particle size could be an important factor affecting total CO2 sequestration capacity, this study investigates the effect of gradation on the CO2 sequestration capacity of the BOF slag under simulated landfill gas conditions. Batch and column experiments were performed with BOF slag using three gradations: (1) coarse (D50 = 3.05 mm), (2) original (D50 = 0.47 mm), and (3) fine (D50 = 0.094 mm). The respective CO2 sequestration potentials attained were 255 mg g-1, 155 mg g-1, and 66 mg g-1. The highest CO2 sequestration capacity of fine BOF slag was attributed to the availability of calcium containing minerals on the slag particle surface owing to the highest surface area and shortest leaching path for the Ca2+ from the inner core of the slag particles.

Rats exposed to 2.45GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3.

In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems.

Gene Expression Profiling in Fish Toxicology: A Review.

In this review, we present an overview of transcriptomic responses to chemical exposures in a variety of fish species. We have discussed the use of several molecular approaches such as northern blotting, differential display reverse transcription-polymerase chain reaction (DDRT-PCR), suppression subtractive hybridization (SSH), real time quantitative PCR (RT-qPCR), microarrays, and next-generation sequencing (NGS) for measuring gene expression. These techniques have been mainly used to measure the toxic effects of single compounds or simple mixtures in laboratory conditions. In addition, only few studies have been conducted to examine the biological significance of differentially expressed gene sets following chemical exposure. Therefore, future studies should focus more under field conditions using a multidisciplinary approach (genomics, proteomics and metabolomics) to understand the synergetic effects of multiple environmental stressors and to determine the functional significance of differentially expressed genes. Nevertheless, recent developments in NGS technologies and decreasing costs of sequencing holds the promise to uncover the complexity of anthropogenic impacts and biological effects in wild fish populations.

Biological evaluation of ultrananocrystalline and nanocrystalline diamond coatings.

Nanostructured biomaterials have been investigated for achieving desirable tissue-material interactions in medical implants. Ultrananocrystalline diamond (UNCD) and nanocrystalline diamond (NCD) coatings are the two most studied classes of synthetic diamond coatings; these materials are grown using chemical vapor deposition and are classified based on their nanostructure, grain size, and sp3 content. UNCD and NCD are mechanically robust, chemically inert, biocompatible, and wear resistant, making them ideal implant coatings. UNCD and NCD have been recently investigated for ophthalmic, cardiovascular, dental, and orthopaedic device applications. The aim of this study was (a) to evaluate the in vitro biocompatibility of UNCD and NCD coatings and (b) to determine if variations in surface topography and sp3 content affect cellular response. Diamond coatings with various nanoscale topographies (grain sizes 5-400 nm) were deposited on silicon substrates using microwave plasma chemical vapor deposition. Scanning electron microscopy and atomic force microscopy revealed uniform coatings with different scales of surface topography; Raman spectroscopy confirmed the presence of carbon bonding typical of diamond coatings. Cell viability, proliferation, and morphology responses of human bone marrow-derived mesenchymal stem cells (hBMSCs) to UNCD and NCD surfaces were evaluated. The hBMSCs on UNCD and NCD coatings exhibited similar cell viability, proliferation, and morphology as those on the control material, tissue culture polystyrene. No significant differences in cellular response were observed on UNCD and NCD coatings with different nanoscale topographies. Our data shows that both UNCD and NCD coatings demonstrate in vitro biocompatibility irrespective of surface topography.

Pulse laser deposited nanostructured ZnO thin films: a review.

This review summarizes the work principles of pulse laser deposition (PLD) apparatus, physical processes like ablation, and plasma plume formation accompanying the deposition of un-doped ZnO from target to substrate material. Various modes of deposition and factors influencing the properties of thin films such as substrate temperature, background gas pressure, laser energy density (laser fluence), target to substrate distance, repetition rate, oxygen partial pressure in deposition chamber, deposition time and post growth annealing which control deposition parameters such as adsorption, desorption, surface diffusion, nucleation, and crystallization/re-crystallization are also discussed in this review. Moreover, various film properties such as morphology, roughness of the film surface, film thickness, grain size, optical transmittance, sensitivity, electrical conductivity, uniformity and electrical resistivity of the deposited ZnO thin films have also been enumerated in the present review.

A review of the genus Paraleptomenes Giordani Soika, 1970 (Hymenoptera: Vespidae: Eumeninae: Odynerini) from the Indian subcontinent,with the description of a new species from the eastern Himalayas.

The genus Paraleptomenes Giordani Soika, 1970 is reviewed for the Indian subcontinent. A new species Paraleptomenes darugiriensis Kumar, Carpenter & Sharma, sp. nov. is described. The male of P. rufoniger Giordani Soika, 1994 is described for the first time. The distribution records of P. humbertianus (de Saussure, 1867), P. miniatus mephitis (Cameron, 1901), P. miniatus miniatus (de Saussure, 1855), and P. rufoniger Giordani Soika, 1994 in the Indian states are augmented. A key to species of the Indian subcontinent and a world checklist of species are provided.

Three new species of the genus Odontomutilla Ashmead, 1899 (Hymenoptera: Mutillidae) from India.

Three new species of velvet ant, Odontomutilla jaferpaloti sp. nov. (India: Karnataka), O. vishwanathi sp. nov. (India: Karnataka), and O. himalayensis sp. nov. (India: Uttarakhand), are described and illustrated. Diagnostic features of these new species, to separate them from similar species are provided. The updated key to the species of India is given.

Discovery of a new species of the genus Cephalotilla Bischoff, 1920 (Hymenoptera: Mutillidae) from India.

A new species, Cephalotilla manikandani Terine, Lelej & Girish Kumar, sp. nov., is described based on female specimens from Southern India. A key to the Oriental species of Cephalotilla Bischoff, 1920 is given.

Whole-genome sequencing of four culturable endophytic bacteria from German hardneck garlic cloves (Allium sativum L.).

We present the whole-genome sequence of four bacterial endophytes associated with German hardneck garlic cloves (Allium sativum L.). Among them, Agrobacterium fabrum and Pantoea agglomerans are associated with plant protection, while Rahnella perminowiae and Stenotrophomonas lactitubi are pathogens. These data will facilitate the identification of genes to improve garlic.

Isolation, whole-genome sequencing, and annotation of two antibiotic-producing and antibiotic-resistant bacteria, Pantoea rodasii RIT 836 and Pseudomonas endophytica RIT 838, collected from the environment.

Antimicrobial resistance (AMR) is a global threat to human health since infections caused by antimicrobial-resistant bacteria are life-threatening conditions with minimal treatment options. Bacteria become resistant when they develop the ability to overcome the compounds that are meant to kill them, i.e., antibiotics. The increasing number of resistant pathogens worldwide is contrasted by the slow progress in the discovery and production of new antibiotics. About 700,000 global deaths per year are estimated as a result of drug-resistant infections, which could escalate to nearly 10 million by 2050 if we fail to address the AMR challenge. In this study, we collected and isolated bacteria from the environment to screen for antibiotic resistance. We identified several bacteria that showed resistance to multiple clinically relevant antibiotics when tested in antibiotic susceptibility disk assays. We also found that two strains, identified as Pantoea rodasii RIT 836 and Pseudomonas endophytica RIT 838 via whole genome sequencing and annotation, produce bactericidal compounds against both Gram-positive and Gram-negative bacteria in disc-diffusion inhibitory assays. We mined the two strains' whole-genome sequences to gain more information and insights into the antibiotic resistance and production by these bacteria. Subsequently, we aim to isolate, identify, and further characterize the novel antibiotic compounds detected in our assays and bioinformatics analysis.

Acute hypotension associated with intraoperative cell salvage using a leukocyte depletion filter during management of obstetric hemorrhage due to amniotic fluid embolism.

Amniotic fluid embolism (AFE) is a rare but catastrophic obstetric complication that can lead to profound coagulopathy and hemorrhage. The role of cell salvage and recombinant human Factor VIIa (rFVIIa) administration in such cases remains unclear. We present a case of AFE and describe our experience with the use of cell salvage and rFVIIa administration during the resuscitation. Cell salvage and transfusion through a leukocyte depletion filter was attempted after the diagnosis of AFE was made, but the attempted transfusion was immediately followed by hypotension and a worsening of hemodynamics. rFVIIa, on the contrary, was used with clinical improvement in coagulopathy and without apparent adverse thrombotic effect.

A taxonomic review of the genus Antodynerus de Saussure, 1855 (Hymenoptera: Vespidae: Eumeninae) from the Indian subcontinent.

The genus Antodynerus de Saussure, 1855 is reviewed from the Indian subcontinent. Three species with one additional subspecies are present, namely Antodynerus flavescens flavescens (Fabricius, 1775), A. f. karachiensis Giordani Soika, 1970, A. limbatus (de Saussure, 1852), and A. punctatipennis (de Saussure, 1853). The parasitic association of strepsipteran insects and the symbiotic association of mites are reported for the first time in the genus Antodynerus. The distribution of A. f. flavescens (Fabricius) and A. limbatus (de Saussure) in the Indian states is augmented. The latter species is newly recorded from China (Tibet). A key to species of the Indian subcontinent is provided.

A new species of the genus Smicromyrme THOMSON, 1870 (Hymenoptera: Mutillidae) from India.

Smicromyrme (Eremotilla) williamsi Terine & Girish Kumar, sp. nov. is described based on a female specimen from Kerala, Southern India. A modified key to the S. coromandelica species-group (females only) is given.

Codelivery of Phytochemicals with Conventional Anticancer Drugs in Form of Nanocarriers.

Anticancer drugs in monotherapy are ineffective to treat various kinds of cancer due to the heterogeneous nature of cancer. Moreover, available anticancer drugs possessed various hurdles, such as drug resistance, insensitivity of cancer cells to drugs, adverse effects and patient inconveniences. Hence, plant-based phytochemicals could be a better substitute for conventional chemotherapy for treatment of cancer due to various properties: lesser adverse effects, action via multiple pathways, economical, etc. Various preclinical studies have demonstrated that a combination of phytochemicals with conventional anticancer drugs is more efficacious than phytochemicals individually to treat cancer because plant-derived compounds have lower anticancer efficacy than conventional anticancer drugs. Moreover, phytochemicals suffer from poor aqueous solubility and reduced bioavailability, which must be resolved for efficacious treatment of cancer. Therefore, nanotechnology-based novel carriers are employed for codelivery of phytochemicals and conventional anticancer drugs for better treatment of cancer. These novel carriers include nanoemulsion, nanosuspension, nanostructured lipid carriers, solid lipid nanoparticles, polymeric nanoparticles, polymeric micelles, dendrimers, metallic nanoparticles, carbon nanotubes that provide various benefits of improved solubility, reduced adverse effects, higher efficacy, reduced dose, improved dosing frequency, reduced drug resistance, improved bioavailability and higher patient compliance. This review summarizes various phytochemicals employed in treatment of cancer, combination therapy of phytochemicals with anticancer drugs and various nanotechnology-based carriers to deliver the combination therapy in treatment of cancer.