Role of bio-flavonols and their derivatives in improving mitochondrial dysfunctions associated with pancreatic tumorigenesis.

Mitochondria, a cellular metabolic center, efficiently fulfill cellular energy needs and regulate crucial metabolic processes, including cellular proliferation, differentiation, apoptosis, and generation of reactive oxygen species. Alteration in the mitochondrial functions leads to metabolic imbalances and altered extracellular matrix dynamics in the host, utilized by solid tumors like pancreatic cancer (PC) to get energy benefits for fast-growing cancer cells. PC is highly heterogeneous and remains unidentified for a longer time because of its complex pathophysiology, retroperitoneal position, and lack of efficient diagnostic approaches, which is the foremost reason for accounting for the seventh leading cause of cancer-related deaths worldwide. PC cells often respond poorly to current therapeutics because of dense stromal barriers in the pancreatic tumor microenvironment, which limit the drug delivery and distribution of antitumor immune cell populations. As an alternative approach, various natural compounds like flavonoids are reported to possess potent antioxidant and anticancerous properties and are less toxic than current chemotherapeutic drugs. Therefore, we aim to summarize the current state of knowledge regarding the pharmacological properties of flavonols in PC in this review from the perspective of mitigating mitochondrial dysfunctions associated with cancer cells. Our literature survey indicates that flavonols efficiently regulate cellular metabolism by scavenging reactive oxygen species, mitigating inflammation, and arresting the cell cycle to promote apoptosis in tumor cells via intrinsic mitochondrial pathways. In particular, flavonols proficiently inhibit the cancer-associated proliferation and inflammatory pathways such as EGFR/MAPK, PI3K/Akt, and nuclear factor κB in PC. Overall, this review provides in-depth evidence about the therapeutic potential of flavonols for future anticancer strategies against PC; still, more multidisciplinary human interventional studies are required to dissect their pharmacological effect accurately.

Development of metal free carbon catalyst derived from Parthenium hysterophorus for the electrochemical detection of dopamine.

Parthenium hysterophorus, one of the seven most hazardous weeds is widely known for its allergic, respiratory and skin-related disorders. It is also known to affect biodiversity and ecology. For eradication of the weed, its effective utilization for the successful synthesis of carbon-based nanomaterial is a potent management strategy. In this study, reduced graphene oxide (rGO) was synthesized from weed leaf extract through a hydrothermal-assisted carbonization method. The crystallinity and geometry of the as-synthesized nanostructure are confirmed from the X-ray diffraction study, while the chemical architecture of the nanomaterial is ascertained through X-ray photoelectron spectroscopy. The stacking of flat graphene-like layers with a size range of ∼200-300 nm is visualized through high-resolution transmission electron microscopy images. Further, the as-synthesized carbon nanomaterial is advanced as an effective and highly sensitive electrochemical biosensor for dopamine, a vital neurotransmitter of the human brain. Nanomaterial oxidizes dopamine at a much lower potential (0.13 V) than other metal-based nanocomposites. Moreover, the obtained sensitivity (13.75 and 3.31 µA µM-1 cm-2), detection limit (0.6 and 0.8 µM), the limit of quantification (2.2 and 2.7 µM) and reproducibility calculated through cyclic voltammetry/differential pulse voltammetry respectively outcompete many metal-based nanocomposites that were previously used for the sensing of dopamine. This study boosts the research on the metal-free carbon-based nanomaterial derived from waste plant biomass.

Myeloid-derived suppressor cells: Bridging the gap between inflammation and pancreatic adenocarcinoma.

Pancreatic cancer has been identified as one of the deadliest malignancies because it remains asymptomatic and usually presents in the advanced stage. Tumour immune evasion is a well-known mechanism of tumorigenesis in various forms of human malignancies. Chronic inflammation via complex networking of various inflammatory cytokines in the local tissue microenvironment dysregulates the immune system and support tumour development. Pro-inflammatory mediators present in the tumour microenvironment increase the tumour burden by causing immune suppression through the generation of myeloid-derived suppressor cells (MDSCs) and T regulatory cells. These cells, along-with myofibroblasts, create a highly immunosuppressive and resistant tumour microenvironment and are thus considered as one of the culprits for the failure of anti-cancer chemotherapies in pancreatic adenocarcinoma patients. Targeting these MDSCs using various combinatorial approaches might have the potential for abrogating the resistance and suppressive nature of the pancreatic tumour microenvironment. Therefore, there is more curiosity in studying the crosstalk of MDSCs with other immune cells during pathological conditions and the underlying mechanisms of immunosuppression in the current scenario. In this article, the possible role of MDSCs in inflammation-mediated tumour progression of pancreatic adenocarcinoma has been discussed.

IL-6 is associated with expansion of myeloid-derived suppressor cells and enhanced immunosuppression in pancreatic adenocarcinoma patients.

Chronic inflammation favours the expansion of myeloid-derived suppressor cells (MDSCs) by secreting pro-inflammatory mediators. The role of MDSCs in mediating immunosuppression in pancreatic adenocarcinoma and in defining a premalignant route from chronic pancreatitis remains unclear. We aimed to study the immunosuppressive potential of all subsets of MDSCs and their correlation with inflammatory cytokines in pancreatic adenocarcinoma and chronic pancreatitis. Relative frequencies of MDSCs, immunosuppressive markers arginase-1 (ARG-1), programmed death-ligand 1 (PD-L1), reactive oxygen species (ROS) and cytokines in circulation and surgically resected local pancreatic tissue of chronic pancreatitis and pancreatic adenocarcinoma patients were analysed by multicolour flow cytometry and cytokine bead array, respectively. Levels of cytokines involved in MDSCs activation were analysed by ELISA, and the immunosuppressive nature of MDSCs was confirmed by T-cell suppression assay. Frequencies of circulating MDSCs and ARG-1, PD-L1, and ROS were significantly higher in pancreatic adenocarcinoma than healthy controls and showed a significant positive correlation with MDSCs burden in cancer tissue. Serum levels of cytokines IL-6, IL-8 and IL-10 were significantly elevated in pancreatic adenocarcinoma. IL-6 serum levels showed a significant positive correlation with frequencies of circulating MDSCs in pancreatic adenocarcinoma patients, and MDSCs mediated suppression of T-cell proliferation in vitro was associated with elevated IL-6 levels in the cell culture medium. Collectively, our results suggest that IL-6 plays a crucial role in the expansion of MDSCs and activating their immunosuppressive nature in pancreatic adenocarcinoma. The relative frequency of MDSCs in circulation can be used as a potential diagnostic biomarker for pancreatic cancer.

Intraoperative tragal and conchal cartilage thickness: Comparative study for cartilage tympanoplasty.

INTRODUCTION: In conditions like recurrent perforations, atelectatic tympanic membrane and poor eustachian tube function, temporalis fascia graft fails to give the desired result. In such cases cartilage is used for tympanoplasty. It was demonstrated that if the thickness of cartilage is reduced to around 0.5 mm, the sound conduction is comparable to that of normal tympanic membrane with excellent mechanical stability. AIM: To intra-operatively measure the mean thickness of tragal and conchal cartilage and compare it for age and sex variations. MATERIAL & METHODS: A total of 114 tragal and conchal cartilage samples of 86 patients were included in the study. Thickness of cartilages was measured intra-operatively after removing the perichondrium from both sides. RESULTS: Out of 58 tragal cartilages, 32 were from males and 26 from females. Mean thickness was 1.18 ± 0.11 mm among males and 1.12 ± 0.14 mm among females. Out of 56 conchal cartilage taken, 29 were from males and 27 females. Mean thickness among males were 1.38 ± 0.13 mm and 1.35 ± 0.08 mm in females. In 28 patients both tragal and conchal cartilage was taken. Mean thickness of both tragal (1.22 mm) and conchal cartilage (1.36 mm) increased with increase in age. Among 16 males in whom both cartilages were taken, mean thickness of tragal cartilage was 1.25 ± 0.11 mm and conchal cartilage was 1.41 ± 0.12 mm. Similarly among 12 females where both cartilages were taken, mean thickness of tragal cartilage was 1.20 ± 0.13 mm and conchal cartilage was 1.35 ± 0.07 mm. CONCLUSION: Sliced cartilage tympanoplasty is a relatively better technique. When using cartilage splitter to get sliced cartilage, ideally thickness of every graft should be known. As it is difficult to measure the exact thickness in every case, so knowing the mean for age and sex for cartilage thickness is important to have an idea of which plates to use for a successful outcome of slicing. We concluded that thickness of tragal cartilage is significantly less than the thickness of conchal cartilage. Also there is significant age related difference between mean thickness of cartilages, both for tragal and conchal cartilage. Surprisingly the difference between thickness in male and female is not statistically different.

The Reactivity of Ambident Nucleophiles: Marcus Theory or Hard and Soft Acids and Bases Principle?

The model reactions CH3 X + (NH-CH=O)M ➔ CH3 -NH-NH═O or NH═CH-O-CH3 + MX (M = none, Li, Na, K, Ag, Cu; X = F, Cl, Br) are investigated to demonstrate the feasibility of Marcus theory and the hard and soft acids and bases (HSAB) principle in predicting the reactivity of ambident nucleophiles. The delocalization indices (DI) are defined in the framework of the quantum theory of atoms in molecules (QT-AIM), and are used as the scale of softness in the HSAB principle. To react with the ambident nucleophile NH═CH-O- , the carbocation H3 C+ from CH3 X (F, Cl, Br) is actually a borderline acid according to the DI values of the forming C…N and C…O bonds in the transition states (between 0.25 and 0.49), while the counter ions are divided into three groups according to the DI values of weak interactions involving M (M…X, M…N, and M…O): group I (M = none, and Me4 N) basically show zero DI values; group II species (M = Li, Na, and K) have noticeable DI values but the magnitudes are usually less than 0.15; and group III species (M = Ag and Cu(I)) have significant DI values (0.30-0.61). On a relative basis, H3 C+ is a soft acid with respect to group I and group II counter ions, and a hard acid with respect to group III counter ions. Therefore, N-regioselectivity is found in the presence of group I and group II counter ions (M = Me4 N, Li, Na, K), while O-regioselectivity is observed in the presence of the group III counter ions (M = Ag, and Cu(I)). The hardness of atoms, groups, and molecules is also calculated with new functions that depend on ionization potential (I) and electron affinity (A) and use the atomic charges obtained from localization indices (LI), so that the regioselectivity is explained by the atomic hardness of reactive nitrogen atoms in the transition states according to the maximum hardness principle (MHP). The exact Marcus equation is derived from the simple harmonic potential energy parabola, so that the concepts of activation free energy, intrinsic activation barrier, and reaction energy are completely connected. The required intrinsic activation barriers can be either estimated from ab initio calculations on reactant, transition state, and product of the model reactions, or calculated from identity reactions. The counter ions stabilize the reactant through bridging N- and O-site of reactant of identity reactions, so that the intrinsic barriers for the salts are higher than those for free ambident anions, which is explained by the increased reorganization parameter Δr. The proper application of Marcus theory should quantitatively consider all three terms of Marcus equation, and reliably represent the results with potential energy parabolas for reactants and all products. For the model reactions, both Marcus theory and HSAB principle/MHP principle predict the N-regioselectivity when M = none, Me4 N, Li, Na, K, and the O-regioselectivity when M = Ag and Cu(I). © 2019 Wiley Periodicals, Inc.

Chronic inflammation during osteoarthritis is associated with an increased expression of CD161 during advanced stage.

Increasing evidence suggests a role of inflammation during the pathogenesis of osteoarthritis (OA). The local and systemic inflammation was studied in 33 patients of different KL grades, grade2 (n = 11), grade3 (n = 6) and grade4 (n = 16). The levels of cytokines, adipokines and matrix metalloproteinases (MMPs) were measured in serum and synovial fluid (SF) by flow cytometry and ELISA, respectively. The frequency of T cells and CD161 expression was measured by flow cytometry. The levels of IL-1ß, IL-6 and IL-10 were significantly higher in sera and SF of patients with OA as compared to healthy control's serum. Higher levels of MMP9 and leptin and lower levels of adiponectin were observed in SF as compared to serum. The MMP9 in SF and MMP13 levels in serum and SF decreased in KL grade 4 cases. In these patients, higher levels of leptin and lower levels of adiponectin were observed in SF versus patients of lower grades. There was increased infiltration of CD8+ T cells in SF of OA cases with decreased frequency in grade 4 cases. The expression of CD161 on T cells was significantly higher in SF than peripheral blood with significant upregulation in grade 4 patients. The CD161 expression had significant positive correlation with IL-17 in the serum of patients. The ROC curves of CD161 expression significantly distinguished grade 2 and grade 4 patients. Collectively, an elevated CD161 expression on T cells in circulation and synovial compartment clearly distinguished lower and higher grade patients warranting studies to assess its role as a contributing factor towards OA progression.

The genus Laggera (Asteraceae) - Ethnobotanical and Ethnopharmacological Information, Chemical Composition as well as Biological Activities of Its Essential Oils and Extracts: A Review.

Most species of the genus Laggera are often used in traditional and folk medicines for the treatment of jaundice, inflammation, leukemia, removing phlegm, bronchitis and bacterial diseases. The essential oils obtained from Laggera plants are rich sources of oxygenated monoterpenes and sesquiterpenes. Among oxygenated monoterpenes, aromatic ether 2,5-dimethoxy-p-cymene is the most abundant and dominant compound of many essential oils of the Laggera species. Till today, to the best of our knowledge, chemical compounds of the essential oils and/or extracts of only eight Laggera species were reported from different countries. Thus, this review presents the chemical compositions and biological activities of the essential oils of these plants studied in thirteen countries. In addition, it discusses the reported ethnobotanical and ethnopharmacological information as well as biological activities of the extracts and some of the isolated compounds of Laggera plants species.

Mesoporous Manganese Oxide Catalyzed Aerobic Oxidative Coupling of Anilines To Aromatic Azo Compounds.

Herein we introduce an environmentally friendly approach to the synthesis of symmetrical and asymmetrical aromatic azo compounds by using air as the sole oxidant under mild reaction conditions in the presence of cost-effective and reusable mesoporous manganese oxide materials.

Exploring PtSO4 and PdSO4 phases: an evolutionary algorithm based investigation.

Metal sulfate formation is one of the major challenges to the emission aftertreatment catalysts. Unlike the incredibly sulfation prone nature of Pd to form PdSO4, no experimental evidence exists for PtSO4 formation. Given the mystery of nonexistence of PtSO4, we explore PtSO4 using a combined approach of an evolutionary algorithm based search technique and quantum mechanical computations. Experimentally known PdSO4 is considered for the comparison and validation of our results. We predict many possible low-energy phases of PtSO4 and PdSO4 at 0 K, which are further investigated in a wide range of temperature-pressure conditions. An entirely new low-energy (tetragonal P42/m) structure of PtSO4 and PdSO4 is predicted, which appears to be the most stable phase of PtSO4 and a competing phase of the experimentally known monoclinic C2/c phase of PdSO4. Phase stability at a finite temperature is further examined and verified by Gibbs free energy calculations of sulfates towards their possible decomposition products. Finally, temperature-pressure phase diagrams are computationally established for both PtSO4 and PdSO4.

Predicting polymeric crystal structures by evolutionary algorithms.

The recently developed evolutionary algorithm USPEX proved to be a tool that enables accurate and reliable prediction of structures. Here we extend this method to predict the crystal structure of polymers by constrained evolutionary search, where each monomeric unit is treated as a building block with fixed connectivity. This greatly reduces the search space and allows the initial structure generation with different sequences and packings of these blocks. The new constrained evolutionary algorithm is successfully tested and validated on a diverse range of experimentally known polymers, namely, polyethylene, polyacetylene, poly(glycolic acid), poly(vinyl chloride), poly(oxymethylene), poly(phenylene oxide), and poly (p-phenylene sulfide). By fixing the orientation of polymeric chains, this method can be further extended to predict the structures of complex linear polymers, such as all polymorphs of poly(vinylidene fluoride), nylon-6 and cellulose. The excellent agreement between predicted crystal structures and experimentally known structures assures a major role of this approach in the efficient design of the future polymeric materials.

Metal-free Carbon Material Derived from Lantana Camara for the Detection and Removal of Ciprofloxacin.

This work reports the preparation of a metal-free nitrogen and sulphur functionalized graphitic carbon sheets from a unique and less expensive precursor Lantana camara, which is a common hazardous weed in India. The synthesized material NS-CN-180 was successfully tested for the adsorption and removal of fluoroquinolone antibiotics ciprofloxacin. The surface morphology and elemental composition of NS-CN-180 were investigated through FESEM and XPS analyses. The SEM data reveals the graphitic sheets stacked onto each other with cavities in between them. The presence of various functional groups was identified through FT-IR spectroscopy and the degree of graphitization was calculated from XRD pattern. The probable mechanism of interaction for ciprofloxacin molecule with NS-CN-180 was also investigated with the help of FT-IR and zeta potential analyses. The fabricated material was found to be excellent for ciprofloxacin detection with a limit of detection value 16.08 nM. Also, the prepared material efficiently removes the 66.2% ciprofloxacin drug in 1 h. Adsorption and desorption experiments were performed to demonstrate the reusability of the material.

Isolation and Characterization of Extracellular Vesicles Derived from Ex Vivo Culture of Visceral Adipose Tissue.

Extracellular vesicles (EVs) are a heterogeneous group of nanoparticles possessing a lipid bilayer membrane that plays a significant role in intercellular communication by transferring their cargoes, consisting of peptides, proteins, fatty acids, DNA, and RNA, to receiver cells. Isolation of EVs is cumbersome and time-consuming due to their nano size and the co-isolation of small molecules along with EVs. This is why current protocols for the isolation of EVs are unable to provide high purity. So far, studies have focused on EVs derived from cell supernatants or body fluids but are associated with a number of limitations. Cell lines with a high passage number cannot be considered as representative of the original cell type, and EVs isolated from those can present distinct properties and characteristics. Additionally, cultured cells only have a single cell type and do not possess any cellular interactions with other types of cells, which normally exist in the tissue microenvironment. Therefore, studies involving the direct EVs isolation from whole tissues can provide a better understanding of intercellular communication in vivo. This underscores the critical need to standardize and optimize protocols for isolating and characterizing EVs from tissues. We have developed a differential centrifugation-based technique to isolate and characterize EVs from whole adipose tissue, which can be potentially applied to other types of tissues. This may help us to better understand the role of EVs in the tissue microenvironment in both diseased and normal conditions. Key features • Isolation of tissue-derived extracellular vesicles from ex vivo culture of visceral adipose tissue or any whole tissue. • Microscopic visualization of extracellular vesicles' morphology without dehydration steps, with minimum effect on their shape. • Flow cytometry approach to characterize the extracellular vesicles using specific protein markers, as an alternative to the time-consuming western blot.

A New Approach for Assessment of Neutrophil Extracellular Traps Through Immunofluorescence Staining in Whole Blood Smears.

Neutrophils, constituting 50%-70% of circulating leukocytes, play crucial roles in host defense and exhibit anti-tumorigenic properties. An elevated peripheral blood neutrophil-to-lymphocyte ratio is associated with decreased survival rates in cancer patients. In response to exposure to various antigens, neutrophils release neutrophil granular proteins, which combine to form web-like structures known as neutrophil extracellular traps (NETs). Previously, the relative percentage of NETs was found to be increased in resected tumor tissue samples from patients with gastrointestinal malignancies. The presence of NETs in peripheral blood is indicative of underlying pathological conditions. Hence, employing a non-invasive method to detect NETs in peripheral blood, along with other diagnostic tests, shows potential as a valuable tool not just for identifying different inflammatory disorders but also for assessing disease severity and determining patient suitability for surgical resection. While reliable methods exist for identifying NETs in tissue, accurately quantifying them in whole blood remains challenging. Many previous methods are time-consuming and rely on a limited set of markers that are inadequate for fully characterizing NETs. Therefore, we established a unique sensitive smear immunofluorescence assay based on blood smears to identify NETs in only as little as 2 µL of whole blood. To identify the NET complexes that have enhanced specificities, this combines the use of various antibodies against neutrophil-specific CD15, NET-specific myeloperoxidase (MPO), citrullinated histone H3 (Cit H3), and nuclear DNA. This protocol offers an easy, affordable, rapid, and non-invasive method for identifying NETs; thus, it can be utilized as a diagnostic marker and targeted through various therapeutic approaches for treating human malignancies. Key features • Characterization of neutrophil extracellular traps in whole blood smears through immunofluorescence staining. • Affordable and quantitative approach to neutrophil extracellular trap detection.

Electrochemical behavior, antimicrobial activities, and effect of temperature on micellization of imidazolium monomeric surfactants.

In the present study, we herein report the conductance behavior, effect of temperature, and chain-length of two environmentally friendly imidazolium cationic capric and stearic surfactants. The conductance behavior has been carried out in aqueous solvent (H2O) at four different temperatures such as 24 °C, 29 °C, 34 °C, and 39 °C. The normal micelles were formed in an aqueous solvent and critical micelle concentration (CMC) can be estimated through conductivity parameters. The expected dependency of the CMC on the alkyl chain length of the 3-(2-(decanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide and 3-(2-(octadecanoyloxy)ethyl)-1-methyl-1H-imidazol-3-ium-bromide was demonstrated. It was observed that the graphs of molar conduct activity v/s square root were not linear, which specifies that the synthesized surfactants behave as weak electrolytes in the dilute solutions. The electrochemical characterization of capric and stearic surfactant modified SPCE was studied in 1mM K3FeCN6 solution. The CS/SPCE and SS/SPCE were shown elevated sensitivity, high stability, and excellent conductivity. Moreover, the antimicrobial behaviors of the synthesized imidazolium cationic surfactants versus various microbial strains were evaluated. Results showed that capric surfactant demonstrated high antibacterial activity against Escherichia coli (MIC > 31.5 µg/mL).

Presentations of Pediatric Emergencies in a Tertiary Teaching Hospital in North India: An Overview.

Pediatric otorhinolaryngological emergencies constitute a major portion in emergency room presentations. The etiology of ENT problems in children is different from those in adults. Most of these can be managed conservatively while some need prompt management at a well equipped centre. To analyze the etiology, clinical profile and line of management of pediatric otorhinolaryngological emergencies. Retrospectively, records of 452 children up to the age of 16 years presenting with ENT complaints were included in the study. Out of 452 patients, 148 presented with aural complaints, 129 had nasal problems and 175 patients with throat complaints. They were classified into Trauma 69 (15.26%), Foreign body 278 (61.50%), Infective 82 (08.14%) and allergic/miscellaneous 23 (05.10%) cases. In aural complaints, foreign body insertion seen in 57 (12.17%) cases while earache in 55 (12.15%) patients. In patients with nasal complaints, foreign body was present in 78 (17.26%) cases. Nasal bleeding and discharge or pain and swelling around nose were the other presentations. Respiratory distress was present in 66 (14.60%) patients while 74 (16.37%) patients came with ingestion of some foreign body. Neck swellings were seen in 20 (04.42%) patients and 15 (03.31%) patients came with history of rashes, feeling of choking or allergic reactions. Surgical intervention after admission was the top most intervention in 202 (44.69%) patients followed by conservative management in 110 (24.33%) patients who were treated and then sent home from emergency centre itself. Minor surgical intervention was sufficient to treat 78 (17.25%) patients without admission. Most common ENT emergency was foreign bodies and these cases need operative intervention. Specialist ENT personnel is needed to handle these cases. Parents must be educated to keep likely causes of these foreign bodies out of reach of growing children and also need to be educated about signs like severe pain, dyspnoea, bleeding or unilateral nasal discharge for timely management.

Senescent chondrogenic progenitor cells derived from articular cartilage of knee osteoarthritis patients contributes to senescence-associated secretory phenotype via release of IL-6 and IL-8.

OBJECTIVES: Despite the presence of chondrogenic progenitor cells (CPCs) in knee osteoarthritis patients they are unable to repair the damaged cartilage. This study aimed to evaluate the oxidative stress, cellular senescence, and senescence-associated secretory phenotype (SASP) in the CPCs derived from osteoarthritic cartilage and compare with the CPCs of healthy articular cartilage. METHODS: Isolated CPCs were characterized based on phenotypic expression of stem cell markers, clonogenicity, and tri-lineage differentiation assay. Production of ROS was measured using DCFDA assay. Cellular senescence in CPCs was assessed by senescence-associated beta-galactosidase assay and expression of senescence markers at the gene level using real-time PCR. Morphological features associated with senescent OA-CPCs were studied using scanning electron microscopy. To study SASP, the production of inflammatory cytokines was assessed in the culture supernatant using a flow-cytometer based cytometric bead array. RESULTS: OA-CPCs exhibited elevated ROS levels along with a relatively high percentage of senescent cells compared to non-OA CPCs, and a positive correlation exists between ROS production and senescence. The morphological assessment of senescent CPCs revealed increased cell size and multiple nuclei in senescent OA-CPCs. These results were further validated by elevated expression of senescence genes p16, p21, and p53. Additionally, culture supernatant of senescent OA-CPCs expressed IL-6 and IL-8 cytokines indicative of SASP. CONCLUSIONS: Despite exhibiting similar expression of stem cell markers and clonogenicity, CPCs undergo oxidative stress in diseased knee joint leading to increased production of intracellular ROS in chondrogenic progenitor cells that support cellular senescence. Further, senescence in OA-CPCs is mediated via the release of pro-inflammatory cytokines, IL-6 and IL-8.

CCR4+ monocytic myeloid-derived suppressor cells are associated with the increased epithelial-mesenchymal transition in pancreatic adenocarcinoma patients.

Among all the cancer-related deaths globally, pancreatic ductal adenocarcinoma (PDAC) accounts for the seventh leading cause of mortality. A dysregulated immune system disrupts anti-tumor immunity by abnormal accumulation of myeloid-derived suppressor cells (MDSCs), but the underlying mechanisms are still inconclusive. To gain new insights into the role of MDSCs in tumor settings, we aimed to determine the mechanism of expansion of various subsets of MDSCs in PDAC patients and their role in promoting invasiveness. We assessed the load of MDSCs, chemokines responsible for the recruitment of MDSCs in PDAC patients by flow cytometry. We investigated the chemokine profile of tumor tissue using qRT-PCR and the status of epithelial-mesenchymal transition (EMT) related markers E-Cadherin, N-Cadherin, Snail, and ZEB1 by qRT-PCR and immunohistochemistry. We found a higher frequency of tumor infiltrated MDSCs in PDAC patients. Chemokine ligands CCL2 and the receptor CCR4 were markedly elevated in the PDAC tumor, while CCR4+ monocytic MDSCs (M-MDSCs) were found significantly elevated in peripheral blood and tumor tissue. In tumor tissue, expression of E-Cadherin was significantly reduced, while N-Cadherin, Snail, and ZEB1 were markedly raised. The frequency of CCR4+ M-MDSCs significantly correlated with the expression of mesenchymal transition markers N-Cadherin, Snail, and ZEB1. Collectively, these results suggest that the CCL2-CCR4 axis plays a crucial role in driving the recruitment of M-MDSCs, which is associated with increased invasiveness in PDAC. This study sheds light on the expansion mechanism of MDSCs, which can serve as a crucial target of future anti-cancer strategies to inhibit tumor cell invasiveness.

Styloid Process; Correlation Between Symptoms, Palpability and Measurements on Three Dimensional Computed Tomography.

Styloid process is a long and slender osseous projection protruding downward, forward and slightly medially from the temporal bone and serves as an anchor point for various muscles associated with the tongue and the larynx. The aim of the present study was to record the length and the angle of Styloid process on three dimensional computed tomography in patients with unilateral symptomatic and palpable styloid process and compare the length and the angle of styloid process of symptomatic side to asymptomatic side on three dimensional computed tomography. 3D-CT face reconstruction were perfomed in all 35 patients (17 females, 18 males of age range 25-69 years). The length of the styloid process and its angulation (transverse and sagittal angles) were measured by means of three dimensional and multiplanar reconstruction images. The length of styloid process on symptomatic side had a mean of 33.61 ± 5.08 mm while on asymptomatic side mean was 31.11 ± 5.02 mm. The mean transverse angle on symptomatic sides had a mean of 72.37° ± 4.48° while on asymptomatic side mean was 74.17° ± 4.48°. The mean sagittal angle seen on symptomatic side was 88.11° ± 5.21° while on asymptomatic side was 87.88° ± 5.03°. Symptomatic side has a longer styloid. Length of the styloid process has a statistical correlation with the symptoms and symptomatic side has a longer styloid. Though there was a difference in transverse and sagittal angulation in symptomatic versus asymptomatic side; but it was not statistically significant. On examination of the opposite asymptomatic side, 5 patients had a palpable styloid process therefore we infer that long styloid process may not always be associated with symptoms. Patients with cervicofacial pain should be evaluated for Eagle syndrome by palpation of styloid process in the tonsillar fossa and further by three dimensional computed tomography (3D-CT). 3D CT is an effective tool in evaluating patients with cervicofacial pain and making a diagnosis of Eagle's syndrome. Therefore, 3D CT should be performed while evaluating patients with these symptoms.