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    Surfactant protein–d amino acid variants and their associations with metabolic, oxidative stress, infection and quality of life parameters in patients with type 2 diabetes mellitus in Pakistan

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    Type 2 diabetes mellitus (T2DM) is prevalent in Pakistan, and often linked to recurrent infections and poor quality of life. Oxidative stress, surfactant protein-D (SP-D), and its rs721917 SNP may contribute to this risk, but no studies have investigated this association in Pakistan. Hence, this study investigated rs721917 SNP variants and their links with metabolic, oxidative stress, infection, and quality of life parameters in T2DM patients. A case-control study was conducted at Aziz Fatimah Hospital, Faisalabad, Pakistan. Using non-probability purposive sampling technique, 170 participants (86 T2DM, 84 Controls; aged 30–65 years) were recruited. Blood samples were tested for SP-D-, Fasting Blood Sugar (FBS), glycated haemoglobin (HbA1c), malondialdehyde (MDA), and superoxide dismutase (SOD) activity. DNA was extracted and amplified by polymerase chain reaction. Sanger sequencing was done to identify the rs721917SNP genotypes. The TC genotype was significantly more prevalent in T2DM patients (p<0.001). SP-D levels were lower in T2DM patients (p=0.014), with higher FBS, HbA1c (both p<0.001), and MDA levels (p=0.012), and reduced SOD activity (p=0.022) compared to controls. SP-D showed significant negative associations with FBS (p=0.001), HbA1c (p=0.032), and MDA (p=0.014). The TC genotype had significantly lower SP-D levels (p=0.040) and SOD activity (p=0.044) compared to TT and CC genotypes. FBS, HbA1c, and MDA levels were higher in TC, followed by CC, versus TT (p=0.006, 0.001, 0.037 respectively). Both TC and CC genotypes showed a three-fold higher oxidative stress risk than TT wild type (p=0.044, 0.041 respectively). Infection rates were higher in T2DM patients (p<0.001), particularly among TC carriers, who had a four-fold higher infection risk (p=0.013). T2DM patients, especially females, showed poor quality of life with Physical Component Summary and Mental Component Summary < 50. No significant impact of SP-D levels and rs721917 was found on quality of life. In conclusion, TC genotype of rs721917 of SP-D was the most common genotype and an independent predictor of oxidative stress and infections in T2DM patients in Pakistani population which were linked with low SP-D levels and SOD activity as well as with high FBS, HbA1c and MDA levels. In addition, T2DM patients also exhibited poor quality of life which was not associated with SP-D levels and rs721917 SNP. Hence, it is plausible to suggest that doing SP-D gene analysis can provide early management and protection against infections in T2DM and further studies are needed to assess the potential use of SP-D as a useful therapy for prevention or treatment of infections in T2D

    Changes in ph of digestive vacuole of plasmodium falciparum treated with pipecolisporin and analogue ii peptide

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    Malaria is a severe and fatal disease caused by Plasmodium spp. and remains one of the leading global causes of morbidity and mortality. The emergence of drug-resistant P. falciparum in various countries has necessitated an effort to discover new antimalarial drugs targeting different pathways. Research on the potential of pipecolisporin and analogue II as an antimalarial agent has remained limited. Therefore, this study aimed to fill this knowledge gap by investigating the antimalarial activity of pipecolisporin and analogue II peptides. The antimalarial potential of pipecolisporin and analogue II against the chloroquine-sensitive strain (3D7) of P. falciparum was assessed based on the calculation of parasitaemia using Giemsa stained-blood smears. The pipecolisporin and analogue II exhibited highly active antimalarial activity with an IC50 value of 0.4770 and 0.1170 μM, respectively. A further investigation focused on the effect of pipecolisporin and analogue II towards the pH of the mid trophozoite stage parasite’s digestive vacuole, employing a flow cytometry-based technique with fluorescein isothiocyanate-dextran (FITC-dextran) as a pH ratiometric probe. The results revealed no increase in pH following pipecolisporin and analogue II treatment. Suggests that pipecolisporin and analogue II might not have the mechanism to alter the digestive vacuole’s pH through the inhibition of V-type H+-ATPase that regulates the acidification of the vacuole. Overall, this study provides crucial evidence of pipecolisporin and analogue II capability as a promising antimalarial candidat

    The effect of tlr4 agonist (crx-527) on il-10 production in mice immunized with bcg-msp-1c

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    Malaria, caused by the Plasmodium parasite, continues to be a significant global health burden, particularly in regions with limited access to healthcare. Current malaria vaccines face challenges of suboptimal efficacy and logistical barriers for widespread implementation. One promising antigen for malaria vaccine development is the C-terminal region of merozoite surface protein 1 (MSP-1C), a conserved fragment of MSP-1, the major surface protein of Plasmodium merozoites, which is essential for red blood cell invasion and evasion of host immune responses. This study evaluates the impact of the Toll-like receptor 4 (TLR4) agonist CRX-527 on IL-10 production in mice immunized with the BCG-MSP-1C vaccine, developed in our laboratory by cloning the MSP-1C antigen with the Bacillus Calmette–Guérin (BCG) vaccine, which is primarily used for tuberculosis (TB) prevention. Treatment groups included PBS-T80, LPS, BCG, and BCG-MSP-1C. The results revealed a significant enhancement of IL-10 production across all groups in both liver and lymph node supernatant samples in the presence of CRX-527. Among these, the BCG-MSP-1C group exhibited the highest IL-10 levels, followed by the BCG, LPS, and PBS-T80 groups. IL-10, an anti-inflammatory cytokine, plays a pivotal role in regulating the immune response, ensuring controlled infection management while minimizing tissue damage. These findings highlight CRX-527’s potential as an effective immune-modulatory adjuvant for malaria vaccine strategies. The incorporation of CRX-527 with the BCG-MSP-1C vaccine offers a dual immunization approach, enabling protection against both malaria and tuberculosis with a single immunization. This strategy could significantly reduce the burden of multiple vaccine doses and improve immunization coverage in resource-limited settings. The study underscores the potential of CRX-527 to enhance vaccine efficacy and promote long-term immunity, supporting its role in advancing cost-effective, dual-purpose vaccine solutions for endemic region

    Vibrotactile fingertip stimulation: fmri investigation of brain activation, ica connectivity, and percent signal change

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    Vibrotactile stimulation is a valuable tool for investigating somatosensory processing, but the effects of varying stimulation frequencies on neural activity and network connectivity are not fully understood. This study investigated the impact of different vibrotactile frequencies on brain activation and functional connectivity within the somatosensory cortex. Twenty healthy, right-handed participants (14 males, 6 females; mean age 25.1 ± 5.01 years) were scanned using 3.0 T MRI during vibrotactile stimulation (30-480 Hz) with piezoelectric vibrator attached at index fingertips. Frequency-specific comparisons revealed greater activation in the right putamen at 90 Hz compared to 120 Hz, potentially related to habituation during motor control learning. Conversely, 120 Hz stimulation, relative to 150 Hz, resulted in significant activation in the left precentral gyrus, right lingual gyrus, right thalamus, right cerebellar lobules 4_5, and right Rolandic operculum, suggesting greater efficacy of lower frequencies. Regarding functional network connectivity, high connectivity between the auditory network (AUN) and visual network (VIN) suggests synchronized activity. Strong functional connectivity between the default mode network (DMN) and VIN suggests sub-networks or clusters within the larger functional network. These interconnected regions (AUN, DMN, VIN), particularly VIN, may form a functional module, with VIN playing a central role in information integration. Moderate positive connectivity between AUN and the sub-cortical domain network (SCN) indicates some synchronized activity. Weak connectivity between the sensorimotor network (SMN) and cognitive control network (CCN) implies minimal functional relationship. Negative connectivity between SCN and SMN suggests anticorrelated activity patterns, possibly reflecting distinct sub-networks. A region of interest (ROI) analysis compared percent signal change between low and high-frequency conditions within the medial frontal gyrus (MFG), paracentral lobule (PaCL), precentral gyrus (PreCG), postcentral gyrus (PoCG), inferior parietal lobule (IPL), and cingulate gyrus (CgG). The Wilcoxon Signed-Rank test revealed significant differences in BOLD signal change between low and high-frequency stimulation in the PaCL (Z = -2.14, p = 0.03, rrb = -0.338), PreCG (Z = -2.46, p = 0.01, rrb = -0.389), PoCG (Z = -2.41, p = 0.01, rrb = -0.381), and CgG (Z = -3.58, p = 0.001, rrb = -0.566), indicating differential processing of high-frequency input. The MFG (Z = -0.97, p = 0.33, rrb = -0.153) and IPL (Z = -1.76, p = 0.08, rrb = -0.278) showed no significant differences, suggesting less direct modulation by vibrotactile frequency. This study provides evidence for distinct neural responses to low and high-frequency vibrotactile stimulation. Observed functional connectivity patterns suggest network cooperation during vibrotactile processing. Our findings demonstrate that activation within S1 and S2 is modulated by vibrotactile frequency, contributing to a deeper understanding of somatosensory processing. Future studies could investigate hub roles, explore different frequency ranges and intensities, and examine clinical implications for sensory processing deficits

    Investigate the effect of ortopedic metal artefact reduction algorithm on dosimetry of imrt prostate with hip prosthesis

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    Prostate cancer is one of the most common cancers among Malaysian men, and radiotherapy—especially intensity-modulated radiation therapy (IMRT)—is a key treatment. However, metal hip implants in some patients can cause artefacts in computed tomography (CT) images, which affect the accuracy of anatomy and radiation dose calculations. This study investigated the efficiency of the Orthopedic Metal Artifact Reduction (OMAR) algorithm by Philips reduces these artefacts and improves dose accuracy in prostate IMRT. A custom male pelvic phantom with a metal hip implant was created using tissue-like materials and treated with a 6 MV photon beam. The radiation doses were calculated using the Eclipse treatment planning system (TPS) and checked using a calibrated thermoluminescent dosimeter (TLD) type 100. The results showed that OMAR significantly reduced image distortion and improved the accuracy of structure outlines and dose delivery. Treatment plans based on OMAR-corrected images had better dose conformity and uniformity. Statistical tests confirmed significant improvements in dose accuracy (p > 0.05) in several organs. Hence, the OMAR algorithm has been proven that it improve both image quality and radiation dose accuracy, making it a valuable tool for radiotherapy planning in patients with metal implants

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