Unraveling the Ties: Type 2 Diabetes and Parkinson's Disease - A Nano-Based Targeted Drug Delivery Approach.

The link between Type 2 Diabetes (T2DM) and Parkinson's Disease (PD) dates back to the early 1960s, and ongoing research is exploring this association. PD is linked to dysregulation of dopaminergic pathways, neuroinflammation, decreased PPAR-γ coactivator 1-α, increased phosphoprotein enriched in diabetes, and accelerated α-Syn amyloid fibril production caused by T2DM. This study aims to comprehensively evaluate the T2DM-PD association and risk factors for PD in T2DM individuals. The study reviews existing literature using reputable sources like Scopus, ScienceDirect, and PubMed, revealing a significant association between T2DM and worsened PD symptoms. Genetic profiles of T2DM-PD individuals show similarities, and potential risk factors include insulin-resistance and dysbiosis of the gut-brain microbiome. Anti-diabetic drugs exhibit neuroprotective effects in PD, and nanoscale delivery systems like exosomes, micelles, and liposomes show promise in enhancing drug efficacy by crossing the Blood-Brain Barrier (BBB). Brain targeting for PD uses exosomes, micelles, liposomes, dendrimers, solid lipid nanoparticles, nano-sized polymers, and niosomes to improve medication and gene therapy efficacy. Surface modification of nanocarriers with bioactive compounds (such as angiopep, lactoferrin, and OX26) enhances α-Syn conjugation and BBB permeability. Natural exosomes, though limited, hold potential for investigating DM-PD pathways in clinical research. The study delves into the underlying mechanisms of T2DM and PD and explores current therapeutic approaches in the field of nano-based targeted drug delivery. Emphasis is placed on resolved and ongoing issues in understanding and managing both conditions.

Noni (Morinda citrifolia) leaf extract incorporated methylcellulose active films: A sustainable strategy for browning inhibition in apple slice packaging.

Methylcellulose, a prominent polysaccharide prevalent in the food sector, was considered to fabricate the active films with glutaraldehyde as a crosslinker and Noni (Morinda citrifolia) Leaf Extract (NLE) as an active agent. FTIR analysis confirms the intermolecular -OH bonding, and SEM micrograms demonstrate methylcellulose active films' homogeneous, dense morphologic appearance. Due to the crosslinking effect of glutaraldehyde and noni leaf extract, tensile strength (41.83 ±â€¯0.134 MPa) and crystallinity (62.91 %) of methylcellulose films were improved. Methylcellulose active films suppress water and moisture uptake at various relative humidities. The inhibition capability against foodborne pathogens and the excellent antioxidant activity [DPPH (93.191 ±â€¯1.384 %) and ABTS (90.523 ±â€¯1.412 %)] of NLE incorporation suggested that food packed in methylcellulose active films were effective against pathogenic and oxidative attacks. During preservation, to ensure the apple slices' nutritional values, they are covered with physiochemically enhanced methylcellulose active films for up to 120 h. The minimum reduction in vitamin C, reducing sugar content, percentage weight loss, pH, and total phenolic content of apple slices preserved in MGN active films at room temperature suggests it is an affordable and efficient replacement to traditional single-use plastic packaging in the cut fruit industry.

Chromene-chromene Schiff base as a fluorescent chemosensor for Th4+ and its application in bioimaging of Caenorhabditis elegans.

The manuscript presents the synthesis of a new di-chromene Schiff base (COM-CH) by combining 7-(diethylamino)-2-oxo-2H-chromene-3-carbohydrazide and 4-oxo-4H-chromene-3-carbaldehyde, and its characterization using various analytical techniques. The probe COM-CH functional group contains a hard donor atom that selectively complexes with Th4+ ions. This report investigated COM-CH's sensing ability towards Th4+ chromogenic and fluorogenic methods in ACN: H2O (8:2, v/v) with Th4+ ions. The COM-CH-Th4+ complex was excited at 430 nm, resulting in a bright emission band at 475 nm with a 45 nm Stokes shift. The COM-CH probe demonstrated the highest performance at pH 4.0 to 8.0, with a sensitivity of 18.7 nM. The complex formation of COM-CH with Th4+ was investigated using NMR, FTIR spectrometry, and density functional theory calculations. The COM-CH and Th4+ are bound with 2:1 stoichiometry and an association constant of 1.92 × 108 M-2. The probe's performance enabled the analysis of monazite sand and water samples for Th4+ content. The probe successfully detected Th4+ content in Caenorhabditis elegans, marking the first Th4+ detection in animal models.

Physicochemical and antioxidant properties of tannic acid crosslinked cationic starch/chitosan based active films for ladyfinger packaging application.

In the present study, cationic starch (CS)/chitosan (CH) incorporated with tannic acid (TA)(CSCT) eco-friendly films were prepared by employing an inexpensive solvent casting technique. Influence of TA on the physicochemical and antimicrobial properties of CS/CH polymer matrix were studied. The FTIR findings and homogeneous, dense SEM micrographs confirms the effective interaction of TA with CS/CH polymer matrix. CSCT-3 active film displayed tensile strength of 26.99±1.91 MPa, which is more substantial than commercially available polyethylene (PE) (12-16 MPa) films. The active films exhibited excellent barrier properties against moisture and water, supported by increased water contact angle values (86.97±0.29°). Overall migration rate of active films was found to be below the permitted limit of 10mg/dm2. The active films showed around 56% of degradation in soil within 15 days. Besides, the active films showed concurring impact against food borne pathogens like E. coli, S. aureus and C. albicans. The CSCT-3 active film presented 90.83% of antioxidant capacity, demonstrating the effective prevention of food oxidation related deterioration. Ladyfinger packaging was inspected to examine the ability of active films as packaging material resulted in effectively resisting deterioration and extending shelf life in comparison with traditional PE packaging.

Evaluation of the outcome of right subumbilical transverse incision approach for the management of complicated appendicitis in paediatric age group - A multi-institutional retrospective study.

Aim: The aim is to evaluate the outcome of right subumbilical transverse incision approach for the management of complicated appendicitis in paediatric age group. Materials and Methods: This is a retrospective multi-institutional study which was conducted in the Department of Paediatric Surgery, I Q City Medical College and Hospital, Durgapur, West Bengal, India and the Department of Paediatric Surgery, Rajiv Gandhi Super Speciality Hospital/Raichur Institute of Medical Sciences, Raichur, Karnataka, India. In this study, a review of 77 paediatric patients operated for complicated appendicitis using a right subumbilical transverse incision approach was done for a period of 3 years (from December 2017 to December 2020). All patients had proven complicated appendicular pathology like appendicular perforation, appendicular abscess or complicated appendicular lumps on ultrasonography or computed tomography scan, which mandated exploration. Results: There was no mortality. Average operative time was 1 h 48 min (ranging from 58 min to 3 h 12 min). Average length of hospital stay was 9 days (ranging from 5 days to 13 days). There was no incidence of fecal fistula. Seventeen (22%) patients developed superficial surgical site infection which subsided with regular dressings. There was no incidence of wound dehiscence or burst abdomen. Five (6.5%) patients required the incision to be extended beyond the midline to the left side to deal with the pathology and to access the entire peritoneal cavity. Nine (11.6%) patients required loop ileostomies, which was fashioned on the lateral aspect of the transverse incision. Only one patient had a doubtful caecal injury which was repaired and loop ileostomy was done. Six patients (7.7%) had adhesive intestinal obstruction postoperatively, of which three required re-exploration. There was no incidence of incisional hernia or any stoma-related complications. Conclusion: Complicated appendicitis is a condition which lacks standardisation of approach for management, and is inherently associated with complications. However, with a more logical incision and intra-operative approach we can keep the complications to minimum and improve outcomes to great extent in those patients requiring surgical intervention. We have been using the subumbilical transverse incision in all sizes of patients ranging from small children to adolescents with excellent results, and we believe that the same approach can be applied even in adult patients in similar clinical scenarios.

A comparative performance evaluation of cephalosporin's drugs for fluoride recognition.

In this manuscript, readily available cephalosporin's drugs cefuroxime axetil (L1) cefpdoxime proxetil (L2), and cefditoren pivoxil (L3) possess dihydrothiazine ring as signaling unit, and -NH groups as the binding site were used for the sensing of fluoride (F-) ions. In the presence of F-, the drug selectively portrayed a naked-eye detectable color change from colorless. The binding constant of 1:1 stoichiometric complex of L1, L2, and L3 with F- was found to be 2.36 × 104 M-1, 2.44 × 103 M-1 and 1.02 × 104 M-1 respectively. The lowest detection limit (LOD) of F- was found to be 11 µM (209 ppb) with drug L1 and L2. The binding mechanism of the drug with F- was studied by 1H and 19F nuclear magnetic resonance (NMR) spectral titration, electrospray ionization mass spectra (ESI-MS) analysis, and density functional theory (DFT) studies. The presence of F- was monitored in various spiked water and Colgate toothpaste samples. Overall, cephalosporin's drug demonstrates a promising potential for the detection of F- ions in the semi-aqueous phase.

Multispectroscopic, virtual and in vivo insights into the photoaging defense mediated by the natural food colorant bixin.

An upsurge in early onset of photoaging due to repeated skin exposure to environmental stressors such as UV radiation is a challenge for pharmaceutical and cosmeceutical divisions. Current reports indicate severe side effects because of chemical or synthetic inhibitors of matrix metalloproteases (MMPs) in anti-skin aging cosmeceuticals. We evaluated the adequacy of bixin, a well-known FDA certified food additive, as a scavenger of free radicals and its inhibitory mechanism of action on MMP1, collagenase, elastase, and hyaluronidase. The anti-skin aging potential of bixin was evaluated by several biotechnological tools in silico, in vitro and in vivo. Molecular docking and simulation dynamics studies gave a virtual insight into the robust binding interaction between bixin and skin aging-related enzymes. Absorbance and fluorescence studies, enzyme inhibition assays, enzyme kinetics and in vitro bioassays of human dermal fibroblast (HDF) cells highlighted bixin's role as a potent antioxidant and inhibitor of skin aging-related enzymes. Furthermore, in vivo protocols were carried out to study the impact of bixin administration on UVA induced photoaging in C57BL/6 mice skin. Here, we uncover the UVA shielding effect of bixin and its efficacy as a novel anti-photoaging agent. Furthermore, the findings of this study provide a strong foundation to explore the pharmaceutical applications of bixin in several other biochemical pathways linked to MMP1, collagenase, elastase, and hyaluronidase.

Mechanism of Cr(VI) reduction by an indigenous Rhizobium pusense CR02 isolated from chromite mining quarry water (CMQW) at Sukinda Valley, India.

Toxicological assessment of CMQW generated due to chromite mining activities at Sukinda Valley has revealed high chromium contamination along with Zn and Fe. The present study focused on the mechanism of chromate reduction by an indigenous multi-metal tolerant bacterium, Rhizobium pusense CR02, isolated from CMQW. The isolated strain has shown resistance up to 520 mg/L of Cr(VI) with an IC50 value of 385.4 mg/L. The highest reduction rate 8.6 × 10-2/h was recorded with 20 mg/L of initial concentration of Cr(VI). Extracellular (3.06 ± 0.012 U/mL), intracellular (3.60 ± 0.13 U/mL), and membrane (1.89 ± 0.01 U/mL) associated chromate reductases were found to be involved for reduction. The extracellular polymeric substances (EPS) produced by the isolate also enhanced reduction activity of 46.32 ± 1.69 mg/L after 72 h with an initial concentration of 50 mg/L. FTIR analysis revealed the involvement of functional groups -OH, -CO, and -NH for Cr(VI) biosorption whereas P=O, -CO-NH- and -COOH interacted with Cr(III). Zeta potential with less negative surface charge favored reduction of Cr(VI). Treatment of CMQW by bacterial isolate detoxified Cr(VI) minimizing chromosomal aberrations in root cells of Allium cepa L., suggesting the role of Rhizobium pusense CR02 as a promising bio-agent for Cr(VI) detoxification.

Impedance Sensor for Real-Time Ammonium Detection Based on MWCNT/ZnO Nanocomposites.

This work reports on the development of an impedance sensor-based real-time-field specific system to monitor aqueous Ammonium (NH4+). The sensing element was fabricated by modifying screen-printed interdigitated electrodes (IDEs) with a hybrid nanocomposite of Multi-Wall Carbon Nanotube (MWCNT) with Zinc Oxide (ZnO) nanocrystals. The NH4+ of the water was monitored, and it exhibited a sensitivity of 67.13 Ω /mM with average correlation coefficients of 0.80. The impedance magnitude ( Ω ) of the NH4+ sensor was unaffected by the presence of Fe2+, Ni2+, K+ and P+ interfering cations. The developed sensor was interfaced with an IoT-enabled NodeMCU microcontroller, enabling a direct method for continuous monitoring of NH4+ concentrations. This integrated system is interconnected to the field-deployed sensor nodes, which provide real-time NH4+ levels to the remote user through web applications.

In vitro studies on the selective cytotoxic effect of luminescent Ru(II)-p-cymene complexes of imidazo-pyridine and imidazo quinoline ligands.

In recent years, Ru(II) complexes have gained high importance in medicinal chemistry due to their significant anti-cancer activities, which are directly related to their DNA binding ability. In this report, the chemistry and cytotoxicity of two new Ru(II) complexes containing imidazole pyridine (Ru-1) and imidazole quinoline (Ru-2) have been studied. The prepared compounds were characterized using infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS), isothermal titration calorimetry (ITC), UV-Vis, and fluorescence spectral techniques. The structural analyses show that the Ru(II) complexes exhibit a 'piano stool' coordination geometry and they are composed of one bound arene, two sigma bonded benzil nitrogen atoms, and labile chlorine linked to Ru(II). The photo-physical properties of these complexes were examined, and they exhibit absorption peaks at 260 nm and 380 nm, which are due to the involvement of intra-ligand charge transitions (ILCT) and metal-to-ligand charge transitions (MLCT), respectively. The binding process of the Ru(II) complexes with DNA and BSA is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with DNA and BSA were found to be 1 × 105 M-1 and 1 × 103 M-1, respectively. In the presence of the Ru(II) complexes, ethidium bromide (EtBr) is competitively displaced from DNA by intercalation of the Ru(II) complexes in DNA and it is well corroborated by viscosity and in silico studies. Both the ligands and Ru(II) complexes were carefully investigated in vitro for cytotoxicity against HeLa, MCF-7, and MDA-MB-231 cells. Surprisingly, both Ru(II) complexes exhibit superior cytotoxicity to cisplatin with a low LD50 value against the examined cancer cells. Besides, an insignificant effect on HEK normal cells (LD50 > 140 µM) was observed.

Pyridine: the scaffolds with significant clinical diversity.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

Iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents.

Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest.

A quinoline-benzothiazole-based chemosensor coupled with a smartphone for the rapid detection of In3+ ions.

A newly designed quinoline-benzothiazole probe 2-((Z)-((E)-benzo[d]thiazol-2(3H)-ylidenehydrazono)methyl)quinolin-8-ol (L) was synthesized by reacting 8-hydroxyquinoline-2-carbaldehyde with 2-hydrazinobenzothiazole and structurally characterized by various spectroscopic techniques. The sensing ability of probe L was studied with various cations using colorimetry, test paper strips, a red-green-blue (RGB) model and UV-visible spectrophotometry in DMSO : H2O (3 : 7, v/v). The pale yellow colour of L turns into orange on contact with In3+ ions, whereas other tested metal ions did not show any change in colour. The probe L exhibits an absorbance band at 360 nm due to ligand-to-ligand charge transfer (LLCT); upon interaction with In3+ ions, it exhibits a band at 445 nm due to ligand-to-metal charge transfer (LMCT). The probe L binds In3+ in a 2 : 1 ratio with an association constant of 8.1 × 105 M-1 and this is established using the Job's and Benesi-Hildebrand (B-H) methods. The probe L can work in the pH range of 4-8 without interfering with other competing ions. It can be used to detect quantities as low as 2.3 ppb and 85 ppb by spectrophotometry and RGB, respectively. The binding mechanism was studied by 1H NMR titration, ESI mass and FT-IR spectral analysis and well supported by theoretical studies. Overall, probe L demonstrates promising potential for the detection of In3+ ions in the semi-aqueous phase and this is its first report as a colorimetric chromogenic probe.

Machine learning-assisted ammonium detection using zinc oxide/multi-walled carbon nanotube composite based impedance sensors.

We report a machine learning approach to accurately correlate the impedance variations in zinc oxide/multi walled carbon nanotube nanocomposite (F-MWCNT/ZnO-NFs) to NH4+ ions concentrations. Impedance response of F-MWCNT/ZnO-NFs nanocomposites with varying ZnO:MWCNT compositions were evaluated for its sensitivity and selectivity to NH4+ ions in the presence of structurally similar analytes. A decision-making model was built, trained and tested using important features of the impedance response of F-MWCNT/ZnO-NF to varying NH4+ concentrations. Different algorithms such as kNN, random forest, neural network, Naïve Bayes and logistic regression are compared and discussed. ML analysis have led to identify the most prominent features of an impedance spectrum that can be used as the ML predictors to estimate the real concentration of NH4+ ion levels. The proposed NH4+ sensor along with the decision-making model can identify and operate at specific operating frequencies to continuously collect the most relevant information from a system.

"Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience.

Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively.

Rapid detection strategies for the ultra-level chemosensing of uranyl ions.

A simple and reliable colorimetric probe N,N'-bis-(4-diethylamino-2-hydroxybenzylidene)-1,10-phenanthroline-2,9-carbohydrazide (L) has been synthesised by reacting 4-(diethylamino)salicylaldehyde with 1,10-phenanthroline-2,9-dicarbohydrazide. The sensing ability of L was studied by its interactions with various f-block metal ions and other selected metal ions from s- and d-block by colorimetry, UV-visible spectrophotometry, and smartphone integrated red-green-blue (RGB) model in DMSO : H2O (7 : 3, v/v). The pale-yellow colour of L turns to wine-red upon interaction with uranyl ions (UO22+) and yellow-orange in the presence of Th4+, Zr4+, Fe3+, and Lu3+ ions. Other tested metal ions did not show any colour change of L. This color change offered a simple, quick, and consistent method for the selective and sensitive visual detection of trace levels of UO22+ ions without any need for sophisticated instruments. Sensor L exhibits two absorption bands at 358 and 389 nm due to ligand-to-ligand charge transfer (LLCT). Upon interaction of L with UO22+ and Th4+ ions, absorption bands are exhibited at 480 nm and 422 nm, respectively, due to ligand-to-metal charge transfer (LMCT). The UV-vis spectral studies indicated the formation of a 1 : 2 ligand-to-metal complex between L and UO22+ with an estimated association constant of 1.0 × 104 M-2. Using L, the concentration of UO22+ can be detected as low as 73 nM and 150 nM by spectrophotometry and RGB methods, respectively, without any interference from other tested ions with an RSD < 5% (n = 3). The binding mechanism was studied by 1H NMR titration, ESI mass, and FT-IR spectral analysis and was well supported by theoretical results. Overall, sensor L demonstrates promising analytical applicability for the detection of UO22+ ions in a semi-aqueous medium.

Phase-Sensitive Vibrationally Resonant Sum-Frequency Generation Microscopy in Multiplex Configuration at 80 MHz Repetition Rate.

Vibrationally resonant sum-frequency generation (VR SFG) microscopy is an advanced imaging technique that can map out the intensity contrast of infrared and Raman active vibrational modes with micron to submicron lateral resolution. To broaden its applications and to obtain a molecular level of understanding, further technical advancement is needed to enable high-speed measurements of VR SFG microspectra at every pixel. In this study, we demonstrate a new VR SFG hyperspectral imaging platform combined with an ultrafast laser system operated at a repetition rate of 80 MHz. The multiplex configuration with broadband mid-infrared pulses makes it possible to measure a single microspectrum of CH/CH2 stretching modes in biological samples, such as starch granules and type I collagen tissue, with an exposure time of hundreds of milliseconds. Switching from the homodyne- to heterodyne-detected VR SFG hyperspectral imaging can be achieved by inserting a pair of optics into the beam path for local oscillator generation and delay time adjustment, which enables self-phase-stabilized spectral interferometry. We investigate the relationship between phase images of several different C-H modes and the relative orientation of collagen triple-helix in fibril bundles. The results show that the new multiplex VR SFG microscope operated at a high repetition rate is a powerful approach to probe the structural features and spatial arrangements of biological systems in detail.

Ultrafast vibrational dynamics of the tyrosine ring mode and its application to enkephalin insertion into phospholipid membranes as probed by two-dimensional infrared spectroscopy.

Enkephalins are small opioid peptides whose binding conformations are catalyzed by phospholipid membranes. Binding to opioid receptors is determined by the orientation of tyrosine and phenylalanine side chains. In this work, we investigate the effects of different charged phospholipid headgroups on the insertion of the tyrosine side chain into a lipid bilayer using a combination of 2D IR spectroscopy, anharmonic DFT calculations, and third order response function modeling. The insertion is probed by using the ∼1515 cm-1 tyrosine ring breathing mode, which we found exhibits rich vibrational dynamics on the picosecond timescale. These dynamics include rapid intramolecular vibrational energy redistribution (IVR), where some of the energy ends up in a dark state that shows up as an anharmonically shifted combination band. The waiting-time dependent 2D IR spectra also show an unusual line shape distortion that affects the extraction of the frequency-frequency correlation function (FFCF), which is the dynamic observable of interest that reflects the tyrosine side chain's insertion into the lipid bilayer. We proposed three models to account for this distortion: a hot-state exchange model, a local environment dependent IVR model, and a coherence transfer model. A qualitative analysis of these models suggests that the local environment dependent IVR rate best explains the line shape distortion, while the coherence transfer model best reproduced the effects on the FFCF. Even with these complex dynamics, we found that the tyrosine ring mode's FFCF is qualitatively correlated with the degree of insertion expected from the different phospholipid headgroups.