Pre-clinical studies comparing the anti-inflammatory potential of artemisinic compounds by targeting NFκB/TNF-α/NLRP3 and Nrf2/TRX pathways in Balb/C mice.

Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds.

The interaction between formylphenoxyacetic acid derivatives (chalcone and flavones) and ionic surfactants: Insights into binding constants, solubilisation and physiochemical properties.

In this study, UV-vis spectroscopy was employed to investigate the interaction between formylphenoxyacetic acid (FPAA) and its derivatives (chalcone and flavones) with ionic surfactants (SDS, CTAB, and DTAB) in different physiological environments. Changes in the physiochemical properties of FPAA chalcone and flavones including binding constants, partitioning constants, and Gibbs free energy were observed which were influenced by the presence of ionic surfactants computed using mathematical models. The solubilization of the targeted compounds in the ionic surfactants was determined through the binding constant (Kb). The results of the present study indicated that electrostatic interactions played a significant role in the solubilization of the targeted compounds in SDS, CTAB, and DTAB. At pH 4.1, FPAA chalcone exhibited stronger binding affinity with SDS compared to CTAB and DTAB. However, at pH 7.4, chalcone showed stronger binding with DTAB compared to SDS, while negligible interaction with CTAB was observed at pH 7.4. The flavones demonstrated stronger binding with DTAB at pH 7.4 compared to SDS and CTAB and it exhibited strong bonding with CTAB at pH 4.1. The negative values of the Gibbs free energy for binding (ΔGb˚) and partitioning (ΔGp˚) constants displayed the spontaneity of the process. However, FPAA chalcone with SDS and FPAA flavones with DTAB furnished positive ΔGb˚, indicating a non-spontaneous process.

Phytogenic-Mediated Zinc Oxide Nanoparticles Using the Seed Extract of Citrullus lanatus and Its Integrated Potency against Multidrug Resistant Bacteria.

In the current research study, zinc oxide nanoparticles (ZnO-NPs) were synthesized via a green synthesis technique using the seed extract of Citrullus lanatus. The study further intended to evaluate the potential synergistic effects of ZnO-NPs with antibiotics against multidrug resistant (MDR) bacteria. It was observed that C. lanatus seed extracts obtained by n-hexane and methanolic solvents revealed the presence of constituents, such as tannins, flavonoids, and terpenoids. Furthermore, the extract of n-hexane displayed the strongest antibacterial activity against Yersinia species (17 ± 1.2 mm) and Escherichia coli (17 ± 2.6 mm), while the methanolic extract showed the maximum antibacterial activity against E. coli (17 ± 0.8 mm). Additionally, the ZnO-NP synthesis was confirmed by ultraviolet-visible analysis with a characteristic absorption peak at 280 nm. The Fourier transform infrared spectroscopy analysis suggested the absorption peaks in the 500-3800 cm-1 range, which corresponds to various groups of tertiary alcohol, aldehyde, amine, ester, aromatic compounds, thiol, amine salt, and primary amine. The scanning electron microscopy spectra of ZnO-NPs demonstrated the presence of zero-dimensional spherical particles with well-dispersed character. Moreover, encapsulation with ZnO-NPs improved the antimicrobial activity of antibiotics against the panel of MDR bacteria, and the increases in the effectiveness of particular antibiotics against MDR bacteria were significant (P = 0.0005). In essence, the synthesized ZnO-NPs have the potential as drug carriers with powerful bactericidal properties that work against MDR bacterial strains. These outcomes are an indication of such significance in pharmaceutical science, giving possibilities for further research and development in this field.

A rare case report of recurrent primary intra-abdominal synovial sarcoma: An unusual manifestation.

Synovial sarcomas are a rare and aggressive subtype of soft tissue sarcomas that typically affects young adults and involves the extremities. Synovial sarcoma of the kidney is a rare and aggressive tumor with a poor prognosis, accounting for only 1% of all renal tumors. The imaging features of this tumor often overlap with those of other renal tumors, and a definitive diagnosis can only be made through immunohistochemical analysis. In this case report, we present the case of a 55-year-old female with left flank pain, who was diagnosed with primary renal synovial sarcoma following a left-sided radical nephrectomy. Despite initial successful surgical intervention, restaging scans showed local recurrence and metastatic disease, which was subsequently managed with 6 cycles of chemotherapy followed by radiation therapy with palliative intent. This case underscores the importance of early detection and aggressive management of rare renal tumors to improve patient outcomes.

PD-L1 is Fascinating but IDO Needs Attention in Non-HCV and Non-HBV-Associated Hepatocellular Carcinoma Patients.

Background/Aim: Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer that is modulated by the immune system. Programmed cell death ligand-1 (PD-L1) has emerged as a novel therapeutic target in various cancers. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is associated with poor prognoses in various cancer types. The aim of this study was to investigate the PD-L1 expression, and clinicopathological features of non-HCV and non-HBV-associated HCC patients, including IDO expression. Patients and Methods: In this study, immunohistochemical analysis was performed to analyze the expression of PD-L1 and IDO. Formalin-fixed paraffin-embedded HCC tumor tissues (n=50) were obtained from the pathology department, at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan between 2005 and 2022. All the patients were HBV and HCV negative. Furthermore, it was a rare group of patients with no previous history of any viral hepatitis. In addition, for categorical and continuous variables chi-square or Fisher exact test and Mann-Whitney U-test was performed. Results: Of 50 tissue specimens, PD-L1+ was observed in 21 [high: 12 (24%), low: 9 (18%)] and PD-L1- was observed in 29 HCC patients. IDO+ was observed in all 50 specimens [high: 42 (84%), low: 8 (16%)]. Additionally, both PD-L1 and IDO had high expression in 11 (22%) patients. While both PD-L1 and IDO had low expression in 2 (4%) patients. Furthermore, in IDO+/PD-L1- group, 20 (69%) out of 29 patients died while in the IDO+/PD-L1+ group, 9 (43%) out of 21 patients died. Conclusion: Evaluation of IDO and PD-L1 expression may add therapeutic advantage in non-HCV and non-HBV-associated HCC patients that overexpress IDO. Further validation in a larger cohort is warranted.

Antibacterial potential and synergistic interaction between natural polyphenolic extracts and synthetic antibiotic on clinical isolates.

Emergence of antimicrobial resistance complicates treatment of infections by antibiotics. This has driven research on novel and combination antibacterial therapies. The present study evaluated synergistic antimicrobial activity of plant extracts and cefixime in resistant clinical isolates. Preliminary susceptibility profiling of antibiotics and antibacterial activity of extracts was done by disc diffusion and microbroth dilution assays. Checker-board, time-kill kinetics and protein content studies were performed to validate synergistic antibacterial activity. Results showed noteworthy quantities of gallic acid (0.24-19.7 µg/mg), quercetin (1.57-18.44 µg/mg) and cinnamic acid (0.02-5.93 µg/mg) in extracts of plants assessed by reverse-phase high performance liquid chromatography (RP-HPLC). Gram-positive (4/6) and Gram-negative (13/16) clinical isolates were intermediately susceptible or resistant to cefixime, which was used for synergistic studies. EA and M extracts of plants exhibited total synergy, partial synergy and indifferent characteristics whereas aqueous extracts did not show synergistic patterns. Time-kill kinetic studies showed that synergism was both time and concentration-dependent (2-8-fold decrease in concentration). Bacterial isolates treated with combinations at fractional inhibitory concentration index (FICI) showed significantly reduced bacterial growth, as well as protein content (5-62 %) as compared to extracts/cefixime alone treated isolates. This study acknowledges the selected crude extracts as adjuvants to antibiotics to treat resistant bacterial infections.

Chitosan Nanoparticles Loaded Poloxamer 407 Gel for Transungual Delivery of Terbinafine HCl.

The current study aimed to develop chitosan nanoparticles (CSNP) loaded poloxamer 407 (P407) gel formulation for transungual delivery of terbinafine HCl (TBN). TBN-CSNP were prepared by nanoprecipitation method and optimized by face-centered central composite design (FCCCD). Optimized TBN-CSNP formulation exhibited a spherical shape with hydrodynamic diameter; zeta potential and entrapment efficiency (EE) of 229 ± 5 nm; 37 ± 1.5 mV; and 75 ± 2% respectively. The solid state of TBN and its compatibility with formulation ingredients were confirmed through XRD and FTIR analysis respectively. TBN-CSNP loaded P407 gel exhibited pseudoplastic rheological behavior having a spreadability of 11 ± 2 g·cm/s. The washability study showed that 40 ± 2% of the gel was eroded after washing 12 times. Drug release from TBN-CSNP- and TBN-CSNP-loaded gel was 84 ± 5% and 57 ± 3%, respectively. The cumulative quantity of TBN permeated from TBN-CSNP-loaded P407 gel and TBN-loaded P407 gel was 25 ± 8 and 27 ± 4 µg/cm2, respectively. The nail uptake study showed that 3.6 ± 0.7 and 2.1 ± 0.3 µg of rhodamine was uptaken by the nail following 2 h topical application of TBN-CSNP loaded P407 gel and TBN loaded P407 gel, respectively. Hence, the developed CSNP-based P407 gel formulation can be a potential carrier for transungual delivery of TBN to topically treat onychomycosis.

Bilateral thoracic outlet syndrome: A rare entity.

Thoracic outlet syndrome (TOS) is the constellations of symptoms produced when the neurovascular structures that traverse the thoracic outlet are compressed. The symptoms are generally due to the compression of the subclavian artery and vein, lower trunk of the brachial plexus as they pass through the thoracic outlet. Diagnosing thoracic outlet syndrome can be difficult because the symptoms and their severity can vary greatly among people. We present a case of 30 years female presenting with arm and scapular pain radiating to hand along with restricted muscle movements; subsequently diagnosed with bilateral thoracic outlet syndrome on CT angiography and confirmed on multiphasic scan.

PREVALENCE OF HEPATITIS C IN DIABETIC PATIENTS: A PROSPECTIVE STUDY.

There is a strong evidence of the relationship between diabetes and hepatitis C however, there are certain gaps in the literature. Therefore, this study was carried out to determine the prevalence of hepatitis C in diabetic patients and risk factors associated with it, to evaluate the presence of possible relationship between hepatitis C and diabetes. Serological testing for anti HCV antibody was carried out on a sample of 100 diabetic patients visiting the diabetic clinic Nishtar Medical College and Hospital Multan. An anti HCV antibody test was carried out on HCV ELISA 3.0 (third generation) kit, locally purchased. Data about demographic information and history of risk factors for HCV was collected from diabetic patients using a structured questionnaire as an experimental tool, after taking informed consent. Data of about 100 non diabetic subjects (volunteer blood donors) was taken from the blood bank of that hospital. Prevalence rate of HCV infection among diabetic patients was recorded 19% and in the control group (non-diabetics) was 3%. Prevalence of HCV infection is higher in type 2 diabetic patients as compared to type 1 diabetic patients (84% vs. 16%). Diabetic patients between age group 46-55 years of age has high prevalence rates (47%) as compared to healthy individuals. Female diabetic patients have higher seropositivity (74%) as compared to male diabetic patients (26%). High prevalence of HCV infection has been reported among diabetic patients with duration of disease = 11 years (47%). Most of the patients were married (95%) and from urban locality (89%) and almost all were poor (99%). HCV positive diabetic patients have also history of blood transfusion (16%), hospital admissions (84%), major surgical procedure (63%), family history of hepatitis C (16%), razor sharing among males (16%) and comb sharing (79%). There was not any I/V drug addict (or history of I/V drug addiction), and tattooing, nose/ear piercing from contaminated needle and toothbrush sharing have not been seen among the participants of research.The results showed that in the present study the prevalence of HCV infection is six times higher in diabetic patients as compared to non-diabetic subjects (control group).

2-{1-[(2-Nitro-benzene-sulfonamido)-meth-yl]cyclo-hexyl}acetic acid.

In the title compound, C(15)H(20)N(2)O(6)S, the C-SO(2)-NH-C torsion angle is 64.54 (14)°. In the mol-ecule, there is a bifurcated N-H⋯(O,O) hydrogen bond, forming S(7) rings. In the crystal, inversion dimers are formed via O-H⋯O hydrogen bonds involving the carboxyl group, so forming R(2) (2)(8) rings. These dimers are further linked via pairs of C-H⋯O hydrogen bonds, forming a C(6) chain propagating along the c-axis direction.

N-Benzyl-N-methyl-3-phenyl-3-[4-(tri-fluoro-meth-yl)phen-oxy]propanamine (N-benzylflouoxetine).

In the title compound, C(24)H(24)F(3)NO, the N-benzyl derivative of fluoxetine {N-methyl-3-[4-(trifluoro-meth-yl)phen-oxy]-benzene-propanamine}, the three aromatic rings A, B and C are inclined to one another by 76.77 (12)° for A/B, 17.05 (14)° for A/C and 89.66 (14)° for B/C. In the crystal structure, mol-ecules are linked via C-H⋯π inter-actions to form one-dimensional chains propagating in the [010] direction.