Therapeutic Importance of Kaempferol in the Treatment of Cancer through the Modulation of Cell Signalling Pathways.

Plant-derived flavonoids are considered natural nontoxic chemo-preventers and have been widely studied for cancer treatment in recent decades. Mostly all flavonoid compounds show significant anti-inflammatory, anticancer and antioxidant properties. Kaempferol (Kmp) is a well-studied compound and exhibits remarkable anticancer and antioxidant potential. Kmp can regulate various cancer-related processes and activities such as cell cycle, oxidative stress, apoptosis, proliferation, metastasis, and angiogenesis. The anti-cancer properties of Kmp primarily occur via modulation of apoptosis, MAPK/ERK1/2, P13K/Akt/mTOR, vascular endothelial growth factor (VEGF) signalling pathways. The anti-cancer property of Kmp has been recognized in several in-vivo and in-vitro studies which also includes numerous cell lines and animal models. This flavonoid possesses toxic activities against only cancer cells and have restricted toxicity on healthy cells. In this review, we present extensive research investigations about the therapeutic potential of Kmp in the management of different types of cancers. The anti-cancer properties of Kmp are discussed by concentration on its capability to target molecular-signalling pathway such as VEGF, STAT, p53, NF-κB and PI3K-AKT signalling pathways. The anti-cancer property of Kmf has gained a lot of attention, but the accurate action mechanism remains unclear. However, this natural compound has a great pharmacological capability and is now considered to be an alternative cancer treatment.

Partial anomalous pulmonary venous connection: state-of-the-art review with assessment using a multidetector computed tomography angiography.

Pulmonary venous anomalies occur as a result of failure in normal embryological development. These anomalies may present as a spectrum ranging from normal variation to partial anomalous pulmonary venous connection (PAPVC) and total anomalous pulmonary venous connection (TAPVC). Though not rare, PAPVC is an uncommon anomaly in which some of the pulmonary veins abnormally connect and drain into the vascular compartments other than the left atrium (LA); however, the others drain normally into the LA. The clinical presentation and severity of affected patients depend on the morphological heterogeneity of the disease. PAPVC associated with other complex conge-nital cardiac diseases present early and are more severe than isolated PAPVC-associated atrial septal defect only. This radiological review gives a detailed description of PAPVC in terms of morphological variability and associated anomalies along with a discussion of the role of multidetector dual-source computed tomography scan in the diagnostic assessment.

Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways.

Polyphenolic flavonoids are considered natural, non-toxic chemopreventers, which are most commonly derived from plants, fruits, and vegetables. Most of these polyphenolics exhibit remarkable antioxidant, anti-inflammatory, and anticancer properties. Quercetin (Qu) is a chief representative of these polyphenolic compounds, which exhibits excellent antioxidant and anticancer potential, and has attracted the attention of researchers working in the area of cancer biology. Qu can regulate numerous tumor-related activities, such as oxidative stress, angiogenesis, cell cycle, tumor necrosis factor, proliferation, apoptosis, and metastasis. The anticancer properties of Qu mainly occur through the modulation of vascular endothelial growth factor (VEGF), apoptosis, phosphatidyl inositol-3-kinase (P13K)/Akt (proteinase-kinase B)/mTOR (mammalian target of rapamycin), MAPK (mitogen activated protein kinase)/ERK1/2 (extracellular signal-regulated kinase 1/2), and Wnt/ß-catenin signaling pathways. The anticancer potential of Qu is documented in numerous in vivo and in vitro studies, involving several animal models and cell lines. Remarkably, this phytochemical possesses toxic activities against cancerous cells only, with limited toxic effects on normal cells. In this review, we present extensive research investigations aimed to discuss the therapeutic potential of Qu in the management of different types of cancers. The anticancer potential of Qu is specifically discussed by focusing its ability to target specific molecular signaling, such as p53, epidermal growth factor receptor (EGFR), VEGF, signal transducer and activator of transcription (STAT), PI3K/Akt, and nuclear factor kappa B (NF-κB) pathways. The anticancer potential of Qu has gained remarkable interest, but the exact mechanism of its action remains unclear. However, this natural compound has great pharmacological potential; it is now believed to be a complementary-or alternative-medicine for the prevention and treatment of different cancers.

Assessment of the Survival Rate of Short Dental Implants in Medically Compromised Patients.

AIM: To assess the survival rate of short dental implants in medically compromised patients. MATERIALS AND METHOD: This follow-up study was conducted on 342 medically compromised patients of both genders (580 dental implants). The failure rate of dental implants was assessed. RESULTS: There were 142 diabetes mellitus patients with 254 dental implants, 108 patients with hypertension with 190 dental implants, 26 patients with mental disabilities with 40 dental implants, 20 oral cancer patients with 36 dental implants, and 46 osteomyelitis subjects with 60 dental implants. There were 60 (10.5%) short dental implant (SDI) failures of which a maximum of 25 (22.7%) were seen with 4 mm diameter. Maximum failure was seen with osteomyelitis patients 8 (13.3%) followed by diabetes mellitus 32 (12.5%). Out of 270 dental implants in 130 control patients, implant failure was seen in 11 (4.07%). There was a significant (p < 0.05) bone loss on follow-up at 6 months, 1 year, and 2 years. CONCLUSION: Medically compromised patients are more prone to dental implant failure as compared to healthy subjects. CLINICAL SIGNIFICANCE: Since medically compromised patients are prone for implant failure, careful selection of cases is necessary.

Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance.

The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not. Their failure to develop tolerance may be explained by their harboring of a loss-of-function mutation in the Rv1258c efflux pump that is linked to macrophage-induced rifampicin tolerance.

Detection and characterization of an albumin-like protein in Leishmania donovani.

The protozoan parasite, Leishmania donovani, undergoes several molecular adaptations and secretes many effector molecules for host cell manipulation and successful parasitism. The current study identifies an albumin-like secretory protein, expressed in its extracellular promastigote forms. A leishmanial complementary DNA sequence of a partial gene has been cloned, and the encoded peptide (14 kD) is used for the production of polyclonal antibody. This targeted antibody identifies a large native protein (66.421 kD), expressed stage-specifically in promastigotes. Through electron microscopic studies, the native protein is found to be localized in the flagellar pocket and flagella and at the surface of the promastigotes. This native protein is purified with the same customized antibody for future characterization and sequencing. The sequence analysis reveals its homology with the mammalian serum albumin. It is evidenced from in silico studies that this albumin-like protein remains associated with long-chain fatty acids while in vitro studies indicate its close association with membrane cholesterol. Since antibody-mediated blocking compromises the parasite infectivity, these leishmanial albumin-like molecules are hereby proposed to play an instrumental role in the infectivity of L. donovani to peripheral blood monocyte cells. Thus, identification and characterization of an albumin-like protein in L. donovani promastigotes may be interpreted as a molecular adaptation candidate. It may be hypothesized that the parasite mimics the mammalian system for importing fatty acids into the intracellular amastigotes, facilitating its host cell infectivity.

A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and their antitubercular activity.

Arylbenzimidazoles have been synthesized as antimycobacterial agents. An efficient synthesis has been developed for 2-arylbenzimidazoles from o-phenylenediamines and aromatic aldehydes in molecular sieves-methanol system. The methodology is straightforward to get 2-arylbenzimidazoles (3a-3z) in excellent yields with high chemoselectivity over 2-aryl-1-benzylbenzimidazoles (4a-4z). All these benzimidazole analogues were evaluated against M. tuberculosis in BACTEC radiometric assay. The compounds 4y and 4z exhibited potential antitubercular activity against M. tuberculosis H37RV, MIC at 16 µM and 24 µM respectively. The best compound of the series i.e. compound 4y was well tolerated by Swiss-albino mice in acute oral toxicity. Compound 4y possessing a diarylbenzimidazole core, can further be optimized for better activity.

Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA topoisomerase-II inhibition.

Naphthoquinones are naturally occurring biologically active entities. Practical de novo syntheses of three naphthoquinones i.e. lawsone (1), lapachol (2), and ß-lapachone (3b) have been achieved from commercially available starting materials. The conversion of lapachol (2) to ß-lapachone (3b) was achieved through p-TSA/Iodine/BF3-etherate mediated regioselective cyclisation. Further, 2-alkyl and 2-benzyllawsone derivatives have been prepared as possible anticancer agents. Four derivatives exhibited significant anticancer activity and the best analogue i.e. compound 21a exhibited potential anticancer activity (IC50=5.2µM) against FaDu cell line. Compound 21a induced apoptosis through activation of caspase pathway and exerted cell cycle arrest at S phase in FaDU cells. It also exhibited significant topoisomerase-II inhibition activity. Compound 21a was found to be safe in Swiss albino mice up to 1000mg/kg oral dose.

First report of molecular characterization and phylogenetic analysis of RoTat 1.2 VSG of Trypanosoma evansi from equine isolate.

Rotat 1.2 variant surface glycoprotein (VSG) is considered to be an important VSG expressed in most of the isolates of Trypanosoma evansi. This makes the molecule an important candidate for both molecular- and serological-based detection of surra. There are ample reports of existence of this gene in isolates from cattle, buffalo, and camel across the world. Of late, there are reports of its absence from a fewer isolates of T. evansi of murine and wildlife origin. Search of literature revealed no reports from horses. The present communication presents the first report of molecular cloning and characterization of Rotat 1.2 VSG from horse isolate of T. evansi from semi-arid region of India. Alongside, the gene was compared with various other isolates across the world. Interestingly, the isolate was found to be closer to camel isolates from Egypt than the other known isolates from India and Kenya.

Dual role of MsRbpA: transcription activation and rescue of transcription from the inhibitory effect of rifampicin.

MsRbpA is an RNA polymerase (RNAP) binding protein from Mycobacterium smegmatis. According to previous studies, MsRbpA rescues rifampicin-induced transcription inhibition upon binding to the RNAP. Others have shown that RbpA from Mycobacterium tuberculosis (MtbRbpA) is a transcription activator. In this study, we report that both MsRbpA and MtbRbpA activate transcription as well as rescue rifampicin-induced transcription inhibition. Transcription activation is achieved through the increased formation of closed RNAP-promoter complex as well as enhanced rate of conversion of this complex to a stable transcriptionally competent RNAP-promoter complex. When a 16 aa peptide fragment (Asp 58 to Lys 73) was deleted from MsRbpA, the resulting protein showed 1000-fold reduced binding with core RNAP. The deletion results in abolition of transcription activation and rescue of transcription from the inhibitory effect of rifampicin. Through alanine scanning of this essential region of MsRbpA, Gly 67, Val 69, Pro 70 and Pro 72 residues are identified to be important for MsRbpA function. Furthermore, we report here that the protein is indispensable for M. smegmatis, and it appears to help the organism grow in the presence of the antibiotic rifampicin.

Tunable Q-factor wavelet transform based identification of diabetic patients using ECG signals.

Diabetes is a chronic health condition that is characterized by increased levels of glucose (sugar) in the blood. It can have harmful effects on different parts of the body, such as the retina of the eyes, skin, nervous system, kidneys, and heart. Diabetes affects the structure of electrocardiogram (ECG) impulses by causing cardiovascular autonomic dysfunction. Multi-resolution analysis of the input ECG signal is utilized in this paper to develop a machine learning-based system for the automated detection of diabetic patients. In the first step, the input ECG signal is decomposed into sub-bands utilizing the tunable Q-factor wavelet transform (TQWT) technique. In the second step, four entropy-based characteristics are evaluated from each SB and elected using the K-W test method. To develop an automatic diabetes detection system, selected features are given as input with 10-fold validation to a SVM classifier using various kernel functions. The 3rd sub-band of TQWT with the Coarse Gaussian kernel function kernel of the SVM classifier yields a classification accuracy of 91.5%. In the same dataset, the comparative analysis demonstrates that the proposed method outperforms other existing methods.

Detection of antibodies against structural proteins of foot-and-mouth disease virus in bovines of western Uttar Pradesh, India.

Foot-and-mouth disease (FMD) is considered as one of the most important contagious viral diseases affecting cloven-footed animals. For effective control of FMD, immunization along with herd immunity is essential in the field conditions. To assure and track the coverage and effectiveness of the vaccination program, the serological studies are very much required after the vaccination program. The present study was aimed to investigate the prevalence of antibodies against structural proteins of FMD virus (FMDV) serotypes of O, A and Asia-1 in seven districts of western Uttar Pradesh, India, and assure the efficacy of vaccination under National Animal Disease Control Program. A total of 308 sera samples were collected from apparent healthy vaccinated cattle and buffaloes from seven districts including Amroha, Baghpat, Bareilly, Bulandsahar, Gautam Budh Nagar, Meerut and Muzaffarnagar of western Uttar Pradesh, India. Determination of antibodies against structural proteins of FMDV was carried out using solid-phase blocking enzyme-linked immunosorbent assay. The protective level of the FMDV serotypes O, A and Asia-1 included in the inactivated trivalent vaccine was 66.55, 48.05 and 47.08% in bovines, respectively. To provide the higher level of protection against the circulating FMDV, the present study recommended the thorough investigation of the immunogenic interaction between the vaccine strains and the field strains. Further investigations should also be conducted with larger sample size and across diverse geographical regions to gain a more comprehensive understanding of herd immunity.

Tunable insulator-metal transition in epitaxial VO2 thin films via strain and defect engineering.

The Metal to Insulator Transition (MIT) in materials, particularly vanadium dioxide (VO2), has garnered significant research interest due to its potential applications in smart windows, memristors, transistors, sensors, and optical switches. The transition from an insulating, monoclinic phase to a conducting, tetragonal phase involves changes in optical and electrical properties, opening avenues in adaptive radiative coolers, optical memories, photodetectors, and optical switches. VO2 exhibits MIT close to 68 °C, thereby requiring tuneable transition temperatures (T c) in VO2 thin films for practical device applications. In this work, we explore the role of strain and defect engineering in tuning the MIT temperature in epitaxial VO2 thin films deposited on c-cut sapphire using Pulsed Laser Deposition (PLD). The study involves tuning the metal-to-insulator transition (MIT) by varying growth parameters, mainly temperature and oxygen partial pressure. Strain engineering along the b-axis helped tune the transition temperature from 65 °C to 82 °C with the out-of-plane b-strain varying from -0.71% to -0.44%. Comprehensive structural and property analyses, including X-ray diffraction (XRD), Reciprocal Space Mapping (RSM), X-ray Photoelectron Spectroscopy (XPS), Raman spectroscopy, and resistivity-temperature (R-T) measurements, were performed to correlate structural properties with T c. Additionally, density functional theory (DFT) calculations were performed using Quantum Espresso within the generalized gradient approximation of the revised Perdew-Burke-Ernzerhof (PBEsol) functional to provide theoretical validity to the experimentally obtained results. Our study provides critical insights into the interplay between strain and oxygen vacancies and their effect on the physical properties of VO2 thin films with DFT calculations supporting the experimental findings.

Arabidopsis Dph4 is an Hsp70 Cochaperone with Iron-Binding Properties.

J-domain proteins (JDPs) are obligate cochaperones of Hsp70s with a wide range of functions in protein homeostasis. Although the J-domain is required for the stimulation of Hsp70s ATPase activity, the functional specificity of JDPs is governed by domains or regions other than the J-domain. Jjj3/Dph4, a class III JDP, is required for diphthamide (DPH) biosynthesis in eukaryotes, including yeast and mammals. Dph4 has a conserved N-terminal J-domain and an uncharacterized C-terminal domain containing a signature CSL zinc finger motif. Previously, we showed that the Dph4 ortholog in Arabidopsis thaliana (atDjC13/AtJjj3/AtDph4) could restore DPH biosynthesis in yeast jjj3Δ mutant in a J-domain-dependent manner. Here, we characterize the C-terminal CSL motif of AtDph4 using yeast genetic and biochemical approaches. The CSL motif of AtDph4 is essential for DPH biosynthesis, and like human Dph4, AtDph4 showed distinct iron-binding activity, which is not present in its yeast counterpart. ScDph4 and AtDph4 proteins exhibit distinct iron-binding capabilities, as evidenced by UV-vis spectrophotometry, SEM-EDS (energy-dispersive spectroscopy function on the scanning electron microscope) and electron paramagnetic resonance (EPR) spectra analyses. Collectively, our data suggests that beyond their role as an Hsp70 cochaperone, Dph4 homologues in complex eukaryotes may have iron-binding abilities, indicating a potential role in iron-sulfur cluster assembly and iron homeostasis.

Above ground tree biomass modeling using machine learning algorithms in western Terai Sal Forest of Nepal.

The monitoring of forest biomass is a crucial biophysical parameter in forest ecosystems, as it provides valuable information for managing forests sustainably and tracking carbon circulation statistics. To achieve sustainable forest management, it is essential to monitor and study forest resources, particularly biomass. This study aimed to model above ground tree biomass (AGTB) using Machine Learning Algorithms (MLAs) in the western terai Sal forest of Nepal. AGTB was calculated using a systematic inventory sample plot, while spectral and textural variables were processed and masked for the study area using Sentinel-2A satellite imagery. Three MLAs namely support vector machine (SVM), random forest (RF), and stochastic gradient boosting (SGB), were employed for modeling with eight categorized variable datasets. Among the MLAs, the RF algorithm with a combination of gray-level co-occurrence matrix (GLCM) and raw bands (RB) dataset variable demonstrated the best performance, with a low RMSE value of 78.81 t ha-1 in the test data. However, the AGTB range from this model ranged from 118.34 to 425.97 t ha-1. The study found that traditional indices, raw bands, and GLCM texture from near-infrared were important variables for AGTB. Nevertheless, the RF algorithm and the dataset combination of GLCM plus raw bands (RB) exhibited excellent performance in all model runs. Thus, this pioneering study on comparative MLAs-based AGTB assessment with multiple datasets variables can provide valuable insights for new researchers and the development of novel approaches for biomass/carbon estimation techniques in Nepal.

mir-98-5p regulates gluconeogenesis and lipogenesis by targeting PPP1R15B in hepatocytes.

Several reports suggest that circulatory miRNAs are deregulated in diverse diseases and used as markers for disease diagnosis and prognosis. Here we show that miR-98-5p, that is down-regulated in the circulation during diabetes, regulates hepatic gluconeogenesis and lipogenesis by targeting PPP1R15B. miR-98-5p overexpression significantly decreased the transcript and protein levels of PPP1R15B in hepatic HepG2 cells and increased p-eIF2α expression and these were prevented in the presence of its inhibitor. Two major hepatic hallmarks during diabetes i.e. hepatic lipid accumulation and glucose output were explored towards physiological relevance. As compared to scramble, overexpression of miR-98-5p decreased the transcript levels of both gluconeogenic and lipogenic genes together with a significant reduction in hepatic glucose production and fat accumulation in HepG2 cells. Using PASTAA to detect common transcription factors regulating these altered genes, CREB emerged as the most significantly enriched transcription factor. While miR-98-5p overexpression did not change the transcript levels of CREB, there was a significant change in its protein levels. While similar effects on gluconeogenic and lipogenic gene expression were detected using the PPP1R15B siRNA, the opposite was observed in the presence of miR-98-5p inhibitor alone. All these suggest that by targeting PPP1R15B, miR-98-5p regulates hepatic steatosis and glucose output; deregulation of which are characteristic hepatic features during diabetes. Therapeutic intervention of the miR-98/PPP1R15B axis might offer a potential strategy to target aberrant hepatic metabolism during diabetes.

Collagen-PVA Films Plasticized with Choline Acetate Ionic Liquid for Sustained Drug Release: UV Shielding, Mechanical, Antioxidant, and Antibacterial Properties.

Collagen and poly(vinyl alcohol) films as topical drug delivery systems were developed by plasticization with glycerol and different concentrations of choline acetate ([Cho]Ac) ionic liquid (IL). The results showed that [Cho]Ac improved the performance of the materials and can serve as an alternative to synthetic plasticizers such as glycerol. Ciprofloxacin (CIP) was used as a model drug to study its release behavior. Ready-to-use films were characterized for their optical opacity, solubility, swelling, mechanical properties, water contact angle, surface morphology, surface roughness, antioxidant, and antimicrobial activities. Moreover, X-ray diffraction and Fourier Transform Infrared (FTIR) studies were carried out for molecular characterization of the films. [Cho]Ac used as a plasticizing agent showed excellent antioxidant properties, mechanical strength, and UV shielding properties. Further, [Cho]Ac improves the roughness and decreases the solubility of films. The in vitro release behavior of CIP was investigated at physiological pH (7.4), and the results showed that CIP was released in a more controlled manner due to the incorporation of [Cho]Ac into the films' matrix, while the films constructed with glycerol exhibited burst release of CIP. Moreover, the films loaded with CIP showed excellent antibacterial activity against Gram-negative (Escherichia coli) as well as Gram-positive (Staphylococcus aureus) bacteria. This study provides insight into the use of choline-based ILs as plasticizing agents for the fabrication of protein-polymer composite films for wound dressing and many other applications.

The Swallow Tail Sign of Substantia Nigra: A Case-Control Study to Establish Its Role in Diagnosis of Parkinson Disease on 3T MRI.

Background and Objectives The loss of swallow tail sign (STS) has been studied for the diagnosis of Parkinson's disease (PD). The study aims to establish the role of STS on high-resolution 3D susceptibility-weighted images (SWI) on 3T MRI in clinically diagnosed cases of PD and compare with control population. Methods and Materials Forty-five patients with clinically diagnosed PD and Parkinson plus syndrome (PPS) formed the study group and were compared with 45 controls without any neurological disease and normal brain magnetic resonance imaging (MRI). Presence or absence of STS was studied on 1-mm thick axial 3D SWI images in bilateral substantia nigra by two radiologists independently, followed by consensus reading. Bilateral absent, unilateral absent, and faintly present STS were considered as absent STS and predicted PD or PPS, and bilateral presence was considered as a positive STS, and was assessed keeping the clinical diagnosis as the gold standard. Results The sensitivity of the absent STS was 75.55%, specificity 97.77%, positive predictive value 97.14%, negative predictive value 80% and accuracy 86.66%, in the diagnosis of PD or PPS, with odd ratio of 132 (confidence interval 15.97-1098.75). Kappa coefficient was 0.80 ( p < 0.001) for both inter- and intrarater agreement, suggesting high reproducibility for the detection of STS. Conclusions Absence of the STS is a good predictor of degeneration of the nigrosome 1 in the substantia nigra in the PD or PPS patients; hence, it can act as a useful marker of these diseases.

Comparison of Recovery Profiles of Patients Undergoing Endoscopic Lumbar Discectomy under Desflurane, Propofol, or Sevoflurane Anesthesia: A Randomized, Prospective, Clinical, Comparative Study.

Background Agents like propofol, sevoflurane, and desflurane having rapid revival of psychomotor and cognitive functions translating into reliable anesthetic recovery are chosen for day care procedures. This prospective randomized comparative study was undertaken to compare the psychomotor and cognitive functions of patients undergoing discectomy under different anesthetic strategies. Methods Seventy-five adult American Society of Anesthesiologists grade I and II patients being operated for endoscopic lumbar discectomy under different anesthetic regimens were enrolled and were subjected to Trieger Dot Test (TDT), Digit Symbol Substitution Test (DSST), and Mini-Mental State Examination (MMSE) preoperatively at specified intervals postoperatively. There emergence and early recovery times, complications, and satisfaction levels were also noted. Results No difference was found in the postoperative TDT and DSST and MMSE scores among the groups at all the time points (15 minutes, 3 minutes, 1 hour, 2 hours, 3 hours, and 4 hours). TDT and DSST demonstrated a tendency to return to baseline by 2nd and 3rd hour postoperatively. Emergence and early recovery times were earlier in the inhalation groups ( p 0.005 and 0.007, respectively). Time required to attain a Modified Aldrete Score of 9, complications, and observed side effects were similar among the groups. Conclusion Patients in the three groups had similar impairments in their psychomotor and cognitive functions which recovered at comparable time periods postoperatively. Emergence and early recovery were, however, faster in the desflurane group.

Assessment of IL-12, mRNA expression, vitamin-D level, and their correlation among the Mycobacterium tuberculosis cases.

BACKGROUND: Tuberculosis (TB) presents serious health related complications caused by the Mycobacterium tuberculosis pathogen. Interleukin 12 (IL-12), plays a central role in T helper 1 (Th1) cells development that are implicated in chronic inflammatory pathogenesis as well as level of 1,25-dihydroxyvitamin D3 can impact on IL-12 mRNA expression at the transcriptional level. METHODS: The present study included clinically confirmed 100 Mycobacterium tuberculosis cases (TB) for assessment of IL-12 mRNA expression and vitamin-D level as well as equal number of healthy controls were also included. RESULTS: In TB cases, overall 13.01-fold higher IL-12 mRNA expression and 30.69 ng/ml vitamin-D level were observed. It was observed that higher expression of IL-12 mRNA expression was linked with TB cases had fever (p < 0.0001), night sweat (p = 0.003), sputum with blood (p = 0.03) as well as decreased vitamin-D level was linked with weight loss (p = 0.01), fever (p < 0.0001), night sweat (p = 0.008), sputum with blood (p = 0.005). TB cases with smoking (p < 0.0001) and alcoholism (p = 0.01, p = 0.0001) had significantly higher IL-12 mRNA expression and lower vitamin-D levels compared to its counterpart. It was observed that TB cases with vitamin-D deficiency, insufficiency, sufficiency had 19.51-fold, 14.64-fold, and 10.54-fold IL-12 mRNA expression respectively (deficiency vs insufficiency; p = 0.0003, deficiency vs sufficiency; p < 0.0001). A negative correlation was observed between IL-12 mRNA expression and vitamin-D level among the TB cases (r = -0.68, p < 0.0001). CONCLUSIONS: Higher IL-12 mRNA expression and lower vitamin-D expression among the TB cases may be responsible for the severity and pathogenesis of TB and alterations in IL-12 mRNA expression and vitamin-D may be influenced by the smoking and alcoholism habit of TB cases.