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Objective: To investigate the effect of Rosa moschata (R. moschata) extract on haloperidol-induced Parkinson’s disease (PD) in rats. Methods: Haloperidol (1 mg/kg) was given to rats intraperitoneally for 3 weeks for induction of PD. R. moschata extract (150, 300 and 600 mg/kg) was administered orally for 21 days. The neuroprotective role of R. moschata leaf extract in PD was explored by performing neurobehavioral tests and RT-PCR analysis and measuring neurotransmitters and oxidative stress biomarkers. Results: An improvement in motor functions and muscle strength was observed in PD rats treated with R. moschata extract. The levels of dopamine, serotonin, noradrenaline, superoxide dismutase, catalase, glutathione, and superoxide dismutase were significantly increased (P < 0.001), whereas acetylcholinesterase and malondialdehyde levels were markedly decreased by treatment with R. moschata extract (P < 0.001). The extract also markedly downregulated the mRNA expressions of IL-1β, α-synuclein, IL-1α, and TNF-α in brain tissue. Moreover, histopathological analysis indicated that neurofibrillary tangles and plaques were noticeably decreased in a dose-dependent manner in PD rats treated with R. moschata extract. Conclusions: R. moschata extract alleviates haloperidol-induced PD in rats by reducing oxidative stress and neurodegeneration. It may be used for management and treatment of PD. However, additional studies are required to confirm its efficacy and molecular mechanisms.

Objective: To investigate the effects of Alpiniae oxyphyllae Fructus (AOF) on renal lipid deposition in diabetic kidney disease (DKD) and elucidate its molecular mechanisms. Methods: The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation. The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells. Cell viability and lipid accumulation were detected by CCK8 and oil red O staining. The expressions of PPARα and fatty acid oxidation-related genes (ACOX1 and CPT1A) were detected by quantitative RT-PCR, Western blot, and immunofluorescence. Furthermore, PPARα knockdown was performed to examine the molecular mechanism of AOF in treating DKD. Results: Network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation showed that the active compounds in AOF targeted PPARα and thus transcriptionally regulated ACOX1 and CPT1A. AOF lowered blood glucose, improved dyslipidemia, and attenuated renal injury in DKD mice. AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation. Additionally, it significantly upregulated the expression of PPARα, ACOX1, and CPT1A in both in vivo and in vitro experiments, which was reversed by PPARα knockdown. Conclusions: AOF may promote fatty acid oxidation via PPARα to ameliorate renal lipid deposition in DKD.

The Clp/Hsp100 family, part of the ATPase associated with various cellular activities (AAA+) superfamily, includes caseinolytic peptidase B (ClpB), a highly conserved protein found in bacteria, fungi, protozoa, and plants. Notably, ClpB is present in all ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. ClpB plays a crucial role in reactivating and disaggregating proteins, enabling pathogens to survive under host-induced stress and conferring thermotolerance to bacterial cells. Infections caused by ESKAPE pathogens are particularly challenging due to their resistance to broad-spectrum antibiotics and biofilm formation, posing a significant global health threat as they are often multidrug-resistant, extensively drug-resistant, and pan-drug-resistant. Given its absence in human cells and its essential role in bacterial survival under stress, ClpB is a promising target for antimicrobial therapy. Targeting Hsp100 family proteins could lead to the development of novel antifungal and antiprotozoal treatments. This review explores the function of ClpB in the survival of ESKAPE pathogens and the protozoan Plasmodium falciparum. Relevant research findings were compiled using academic databases, and data analysis was performed using Clustal Omega Multiple Sequence Alignment and Boxshade tools.

Objective: To characterize mosquito larval habitats and the influence of meteorological factors on their prevalence, and to suggest alternatives for vector control in Makkah Al-Mukarramah. Methods: A mosquito survey was conducted within the 16 municipalities of Makkah Al-Mukarramah, from November 2022 to October 2023. The characteristics of larval habitats used by all reported species as oviposition sites were determined. Seasonal house, container, and breteau indices were used to determine larval abundance. Results: 16 Species belonging to five genera [Aedes (3 spp.), Anopheles (3 spp.), Culex (8 spp.), Culiseta (1 sp.), and Lutzia (1 sp.)] were collected. A total of 185 608 potential mosquito larval habitats were surveyed. Of these, 95 853 (67.4%) were Aedes, 45 522 (32%) were Culex, 718 (0.5%) were Anopheles, and 38 (0.03%) were other species; 154 726 (83.4%) were water sources for mosquito larvae, and among these sources, 7 663 (5.0%) were positive for larvae, with 45.9% indoors and 54.1% outdoors. Most of the positive larval habitats were recorded in Al-Shawqiya (1 093, 14.3%), Al-Sharayia (1 003, 13.1%) and Al-Umrah (984, 12.8%). A total of 142131 mosquito larvae and pupae were collected. The majority number of positive residences for all mosquito larvae was observed in January 2023 (1 658, 21.6%). Conclusions: New appropriate alternatives for vector control are proposed, such as mechanical, biological, and environmental control.

Objective: To investigate the prevalence, mechanisms, and trends of knockdown resistance (kdr) in Anopheles (An.) culicifacies and its impact on the efficacy of organochlorine and other insecticides. Methods: A systematic review was conducted based on PRISMA guidelines, extracting data from biooan.org, Embase, ProQuest, PubMed, Scopus, and Web of Science without a time limit until the end of 2022. Articles meeting the inclusion criteria were assessed using the STROBE checklist. Data on kdr mutations, insecticide resistance, and effectiveness were analyzed across eight selected studies from various regions. Results: The review revealed widespread kdr-mediated resistance in An. culicifacies, primarily against dichloro-diphenyl-trichloroethane (DDT), persisting even decades after discontinued use. Key kdr mutations, including L1014F and L1014S, were identified. Resistance to deltamethrin was less stable, with increased sensitivity observed after short-term discontinuation. The findings underscore the vector's sustained resistance to organochlorine insecticides and relative sensitivity to pyrethroids. Conclusions: Stable kdr resistance in An. culicifacies to organochlorine insecticides highlights the need for periodic susceptibility assessments and strategic rotation or combination of insecticides to combat malaria effectively and prevent the development of resistance.

Objective: To ascertain the prevalence and distribution of malaria parasites among the three monkeys species from three provinces in Sumatra Island, Indonesia. Methods: Infections with Plasmodium spp. were determined morphologically from the blood smears which were stained with Giemsa solution and molecularly through nested polymerase chain reaction (PCR) in DNA samples from 68 primates, which were captured at three locations: Jambi (Bungo district), Bengkulu (Muko-Muko district), and Riau Islands (Lingga district). Results: Out of 68 samples analyzed, 46 were positive for various Plasmodium species, including Plasmodium knowlesi, Plasmodium cynamolgi, Plasmodium inui, and Plasmodium coatneyi. Over one-third of the population exhibited multiple infections, with Plasmodium inui being the most predominant strain. Conclusions: The high prevalence of multiple malaria infections in monkeys, coupled with the rising reports of primate malaria cases in human raises questions about the potential for human transmission. These findings emphasize the necessity for ongoing monitoring and endeavors to comprehend and alleviate the risk of zoonotic malaria transmission, particularly in areas experiencing environmental changes.

Objective: To assess the protective effects of trigonelline against spinal cord injury (SCI) in rats. Methods: Rats (Sprague-Dawley, male) were randomly assigned to seven groups (n=15 per group): normal, sham, SCI control (1% DMSO), methylprednisolone (30 mg/kg), and trigonelline (50, 100, and 200 mg/kg). Rats received respective treatment daily for 28 days. SCI was induced by using a temporary aneurysm clip. Behavioral, biochemical, and histological analyses were performed to investigate the neuroprotective effect of trigonelline. Results: Trigonelline (100 and 200 mg/kg) treatment effectively (P

Objective: To determine the incidence, risk factors, antibiotic resistance patterns, and outcomes of various nosocomial infections in Intensive Care Unit (ICU) patients. Methods: The present prospective observational study was conducted in the multidisciplinary ICU of a tertiary care hospital for 6 months. Incidence, risk factors, and outcome parameters were calculated using Mann Whitney U test, Chi-square test, and stepwise univariate and multivariate logistic regression analysis. Results: The overall incidence of nosocomial infections was 23.5% (74/314). Ventilator-associated pneumonia was the most common infection (54.1%, 52/96), followed by catheter-related bloodstream infections (22.9%, 22/96). Stress ulcer prophylaxis (aOR 7.691, 95% CI 2.202-26.860, P=0.001), endotracheal intubation (aOR 3.251, 95% CI 1.251-8.420, P=0.015), Foley’s catheter (aOR 11.917, 95% CI 1.335-106.410, P=0.027), and ICU stay > 7 days (aOR 30.915, 95% CI 10.062-94.980, P=0.001) were statistically significant risk factors associated with nosocomial infection in ICU patients. Gram­negative bacteria showed a high degree of resistance to most of antibiotics except colistin and tigecycline. Infected group's mortality was significantly greater than the uninfected group (21.62% vs. 5.83% P

Objective: To investigate the toxicity and effect of the extract on some complications of diabetes in Wistar rats. Methods: Type 2 diabetes was induced by a combination of a high-fat diet and streptozotocin (35 mg/kg, i.p.). Aqueous extract of Asparagus africanus (EAA) was prepared and administered (p.o.) for 28 d to groups of diabetic rats as well as to groups of normal rats for toxicity. Fasting blood glucose levels, inflammatory cytokines, and lipid profiles were assessed in diabetic rats. Body and organ weight as well as liver and kidney functions were examined to assess the sub-acute toxicity. Results: EAA for 28 d did not affect the body weight, the weight of the liver, kidney, and heart as well as the serum level of aspartate aminotransferase, alanine aminotransferase, urea, uric acid and creatinine in normal rats. In diabetic rats, the administration of EAA significantly lowered hyperglycemia, reduced interleukin (IL)-6, IL-1β, and tumour necrosis factor-α levels, and increased the level of IL-10. EAA also lowered cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and augmented high-density lipoprotein cholesterol in the serum. As a result of the anti-lipidemic effect, EAA reduced the atherogenic index, Castelli indices, and atherogenic coefficient in diabetic rats. EAA showed the presence of flavonoids, alkaloids, tannins, saponins, terpenes, and steroids. Conclusions: The findings of this study demonstrated that EAA is safe. It has the potential to reduce the glucose level and the risk of inflammation and atherogenesis in diabetic patients.

Originally discovered in 1965 in Maharashtra, India, the Chandipura virus has become a serious hazard to public health, especially in rural areas. Acute encephalitis syndrome, which mostly affects children and has a high death rate, has been associated with Chandipura virus, an arbovirus largely spread by sandflies (Phlebotomus spp.). The virus was first thought to be a benign infection, but after many fatal outbreaks, most notably in Gujarat (2005 and 2024) and Andhra Pradesh (2003), it has come to light. The aggressiveness of the virus is highlighted by the quick development from fever to severe neurological symptoms, such as seizures and coma. Public health initiatives concentrate on vector management and supportive care because there is no particular antiviral medication or vaccine available. Recently, Gujrat has witnessed the biggest outbreak of Chandipura virus in 2024 and it may become a big health concern. This paper discusses about Chandipura virus and its recent cases. The virus’s propagation, which is made worse by climate change, makes future outbreaks of the virus more likely. The epidemiology, transmission, and clinical consequences of Chandipura virus are highlighted in this review, along with the necessity of more research, monitoring, and public health readiness to lessen its effects.

Objective: To examine the effect of fruit extracts of Opuntia ficus-indica on epinephrine-induced myocardial injury in rats. Methods: Rats were pre-treated with hydroalcoholic and anthocyanin-rich extracts (250, 500, and 1 000 mg/kg) orally for 16 days. Epinephrine (2 mg/kg) was injected subcutaneously on days 15 and 16. Then ECG, heart rate, RR interval, cardiac histopathology, and serum parameters of cardiac damage and oxidative stress were evaluated. Results: Pretreatment with the hydroalcoholic and anthocyanin-rich extracts of Opuntia ficus-indica at doses of 500 and 1 000 mg/kg reversed epinephrine-induced changes in ECG, heart rate, RR interval, and cardiac histopathology, and attenuated creatine phosphokinase-MB activity and malondialdehyde level. The extracts at all doses diminished heart weight, lactate dehydrogenase, and aspartate aminotransferase, and also elevated total antioxidant capacity. However, 1 000 mg/kg of the anthocyanin-rich extract was more effective than the hydroalcoholic extract. Conclusions: Supplementation with fruit extracts of Opuntia ficus-indica, especially anthocyanin-rich extract, could protect against epinephrine-induced cardiac injury in rats by alleviating electrocardiographic, biochemical, histopathological, and oxidative stress parameters, and may be used in the treatment of cardiovascular diseases.

Objective: To investigate the antioxidant, antimicrobial, and anticancer effects of Achillea filipendulina. Methods: Phytochemical content was analyzed by GC-MS. Antioxidant activity was assayed by DPPH, total antioxidant status, total oxidant status, and iron reduction tests. Antimicrobial activity was assessed using the MIC assay. Anticancer activity was detected via MTT assay, followed by analysis of the apoptotic process using annexin V and caspase 3/7. miR-519d and Dvl-1 expression were assessed by RT-PCR, and molecular docking analysis was also performed. Results: The ethanol extract of Achillea filipendulina showed the strongest anticancer effect. A significant increase in miR-519d expression was observed in HT29 cells, while a decrease in Dvl-1 expression was noted. DPPH, FRAP, total antioxidant status, and total oxidant assays showed high antioxidant activity. The hexane and ethanol extracts were effective against Streptococcus mutans (MIC

Objective: To investigate whether urinary dipstick proteinuria or urine protein creatinine ratio (UPCR) could predict leakage in children with dengue virus infection. Methods: This was a prospective cross-sectional study. A total of 141 hospitalized patients with confirmed dengue virus infection were enrolled from three hospitals in Thailand. Once daily, complete blood count, serum albumin, and random morning urine dipstick protein were collected from the day of admission to the day after defervescence. Morning UPCR was only measured in patients from one hospital due to logistic reasons. Results: There were 81 and 60 patients in the dengue fever (DF) and DHF groups, respectively. The proportion of patients with proteinuria detected using urine dipstick in the DHF group was higher than that in the DF group from Day-1 (one day before defervescence) to Day +1 (one day after defervescence). Urine dipstick for proteinuria of ≥1+ had sensitivity and specificity of 12.8% and 94.4% on Day-1, and 18.9% and 98.6% on Day 0 (the day of defervescence) to differentiate DHF from DF. For UPCR, cut-off values of approximately 0.2 g/g from Day-2 to Day+1 yielded a sensitivity of 71.6%-94.4% and a specificity of 55.6%-100% in differentiating between DF and DHF. Conclusions: Dipstick proteinuria of ≥1+ on Day-1 to Day+1 after defervescence had poor sensitivity but good specificity in differentiating DHF from DF. UPCR performed better but was less convenient and more expensive than urine dipsticks.

Objective: To evaluate the effects of primary anti-dengue virus envelop protein domain 3 (DENV-ED3) antibodies on secondary heterotypic anti-DENV ED3 antibody responses and the status of anti-DENV antibody responses against multivalent DENV ED3s in mice. Methods: Four different DENV-ED3s were purified and their biophysical characteristics were confirmed. Swiss albino mice aged 3-4 weeks were immunized with four different DENV-ED3s and the anti-ED3 IgG responses were determined by ELISA. Results: Firstly, the primary 1ED3-2ED3-3ED3 cross-reactive anti-DENV1 ED3 response boosted the secondary anti-2ED3 and anti-3ED3 antibody responses. In contrast, primary anti-2ED3 and anti-3ED3 antibodies neither had cross-recognition of 1ED3, nor had any effect on secondary anti-1ED3 response. Besides, the strict serospecificity of the anti-4ED3 sera did not affect other secondary anti-DENV ED3 responses. Secondly, 1ED3, 2ED3, and 3ED3 were co-dominantly immunogenic in trivalent ED3 formulations. However, the poorly immunogenic 4ED3 became almost non-immunogenic when injected after or together with 2ED3 and 3ED3, but showed slightly increased immunogenicity when injected with 1ED3, suggesting an adjuvanticity of 1ED3 on 4ED3’s immunogenicity. Conclusions: Although DENV1~4 ED3s share similar sequence homologies and structures, their immune induction potentials differ significantly in terms of immune magnitude, sero-specificity, and sero-cross-reactivity. Such intrinsic features of DENV1~4 ED3s may lead to ‘antigen interference’, limiting both the understanding of dengue etiology and the success of dengue vaccine development, which needs to neutralize all four DENV serotypes equivalently.

Objective: To investigate the genetic diversity and population structure of the helminth intermediate host, Anentome (A.) helena, populations from northern Thailand and reveal the effect of parasitic infection on snail host populations. Methods: A. helena was collected throughout river drainages from northern Thailand and investigated for larval trematode infection. Seventy-three A. helena specimens were used to examine and re-construct the molecular phylogenetics (neighbour-joining, maximum likelihood, and Bayesian inference methods), genetic diversity, and population structure based on the concatenated datasets of COI and 16S rRNA (1 178 bp). Results: The infection of zoogonid cercariae, heterophyid metacercariae, and echinostome metacercariae in the snail was found from 2 localities, including Mae Sa and Mae Pu Kha populations, with a total prevalence of 6.7% and 16.3%, respectively. The phylogenetic tree and haplotype network revealed three main clades and three haplogroups for each region (COI and 16S rRNA). High levels of genetic diversity in terms of haplotype diversity were found in parasitic infected populations. Conclusions: This is the first time that Echinostoma mekongi has been discovered from A. helena in northern Thailand. The results also showed that parasitic infection can affect the population genetic structure of the snail intermediate host, A. helena. Moreover, habitat and historical demographic changes could be other important factors that can affect the degree of population genetic structure in A. helena. Understanding the population structure of intermediate host species can inform parasite transmission dynamics and is useful for the creation of effective public health management strategies.

Objective: To evaluate the anti-inflammatory effect of black cumin seed oil (BCSO) and its nanoemulsion on lipopolysaccharide (LPS)-induced liver injury in mice. Methods: LPS-induced acute liver injury mouse model was used to evaluate the effects of BCSO and its nanoemulsion formulation on liver function. Hepatic inflammatory markers including Toll-like receptor 4 (TLR4), interleukin(IL)-1β, heme-oxygenase 1, BAX, and BCL-2 were assessed using real-time PCR. Additionally, protein levels of reduced glutathione, tumor necrosis factor-α, and IL-6 were measured using ELISA, and histological analysis was performed. Indomethacin was used as a standard positive control for comparison. Results: BCSO reduced LPS-induced liver injury and exhibited strong anti-inflammatory effects by downregulating the expression of TLR4, IL-1β, IL-6, tumor necrosis factor-α, and heme-oxygenase 1. Additionally, BCSO demonstrated antioxidant properties by increasing reduced glutathione protein levels and decreasing key apoptotic markers BAX and BCL-2 in hepatocytes. The nanoemulsion formulation further enhanced these anti-inflammatory, antioxidant, and anti-apoptotic effects, and histological examination confirmed this effect. Combining BCSO with indomethacin at a lower dose improved efficacy, thereby reducing its potential side effects. Conclusions: The investigation reveals the anti-inflammatory impact of BCSO and its nanoemulsion formulation on LPS-induced liver oxidative stress, inflammation, and apoptosis.

Rationale: Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe complication of dengue virus infection, associated with high mortality. We report a case of a 9-week primigravida presenting with high grade fever spikes and a positive Dengue NS1 antigen. The patient exhibited worsening clinical parameters, including cytopenias. Patient concerns: A primigravida at 9th week of gestation and this condition has limited diagnostic modalities and treatment options for HLH. Diagnoses: HLH secondary to dengue hemorrhagic fever. Outcomes: Intravenous steroids were initiated with monitoring of laboratory and clinical parameters. The patient recovered successfully after initiation of intravenous steroids. Oral steroids were subsequently tapered over an next eight-week period, leading to a successful recovery. Lessons: This case is unique due to the interplay between dengue virus infection, HLH, and early pregnancy, characterized by overlapping clinical symptoms and limited treatment options. Prompt initiation of intravenous steroid therapy resulted in significant clinical improvement. This case highlights the critical importance of early identification and treatment of dengue associated HLH to reduce mortality. Furthermore, it underscores the urgent need for focused research on HLH in pregnant patients, particularly in low and middle income countries.

Objective: To assess prevalence and factors associated with soil-transmitted helminth (STH) infections among rural school children. Methods: This school-based survey applied a cross-sectional design which included children aged 6-14 years enrolled in 12 elementary schools in Banjarwangi, Garut, West Java Province. Stool and blood samples were collected from 388 randomly selected students to examine the STH infections and anemia status, respectively. Anthropometric assessment was performed to profile nutritional status. A structured questionnaire was employed to collect socio-demographic and school performance data. Multivariable logistic regression models were built to assess the factors associated with STH infections in school children. Results: Among 386 schoolchildren, 9.8% children were positive for one or more STH infections, predominantly Trichuris trichiura (9.0%), with males (n=23), significantly more infected than females (n=13) (5.9% vs. 3.4%, P=0.04). The most infected age group was 6-10 years (n=25, 6.5%). The prevalence of STH infection was significantly higher among students that practicing open defecation (n=22, 5.7%) (P=0.03). The odds risk of STH infections was associated with practicing open defecation (aOR 2.54, 95% CI 1.17-5.53, P=0.02). Conclusions: The findings from this study demonstrate the persistent STH transmission among children underscoring the need for sustained post-MDA intervention strategies in resource-limited settings.

Rationale: Dengue fever is a mosquito-bome viral infection, which commonly presents as an acute febrile illness. As the number of cases increases, rare manifestations including neurological manifestations are occasionally encountered. Patient concerns: A 20-year-old female presented with fever for 3 days with slurring of speech and unsteady gait, which were developed from the third day of illness. On examination, she had bilateral cerebellar signs. Dengue non-structural protein 1 antigen and dengue IgM in serum were positive. Her cerebrospinal fluid analysis and magnetic resonance image brain were normal. Diagnosis: Dengue cerebellitis. Intervention: Supportive management with fluids including oral rehydration solutions and intravenous fluids and paracetamol. Outcome: Cerebellar symptoms and signs completely resolved by the 20th day of illness. Lesson: Dengue cerebellitis is an unusual neurological manifestation of dengue infection.

The use of insecticides remain the most effective vector control approach for mosquito borne diseases like malaria, dengue fever, chikungunya, and Zika virus disease; however, their increasing resistance has complicated the management. Mutations in kdr, ace-1/ace-2, rdl, and nAChR, are involved in target-site mediated resistance and prevent the binding of pyrethroids and dichlorodiph enyltrichloroethane, organophosphorus pesticide, carbamates and cyclodienes, respectively. Here, we review the current knowledge on target-site mediated insecticidal resistance mechanisms in major mosquito vectors and the techniques used to identify these mutations. The results showed that kdr mutations are frequently reported in mosquito species, indicating the overuse of pyrethroid in mosquito control. Report on ace mutations is very limited, primarily detected in Anopheles and Culex, with extremely low detection rate in Aedes, despite the wide application of organophosphates in their control. Notably, reports of rdl mutations and changes in nAChR are rare, which provides an opportunity to exploit these target sites, particularly in the event of disease outbreaks. Among various detection methods such as RFLP, TaqMan, Multiplex PCR and FRET, allele-specific PCR is mostly employed, especially in detecting kdr mutation. However, allele-specific PCR cannot detect novel mutation. As a result, there is an urgent need to develop a scalable, cost-effective tool that can be widely applied especially as these mutations are genetic markers for early detection of insecticide resistance. Robust monitoring methods remain critical to manage insecticide resistance and effective control of mosquito-borne diseases.

Objective: To investigate and compare the demographic characteristics, clinical findings, and laboratory results of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients, among Turkish citizens, and foreign nationals. Methods: This study included patients aged 18 and over, both Turkish citizens and foreign nationals, diagnosed with PTB or EPTB between 2016 and 2022. All patients were divided into PTB and EPTB group, and demographic characteristics, clinical findings, and laboratory results were compared. Patients with both PTB and EPTB were not included in the comparison. Multivariate logistic regression analysis was conducted to identify potential risk factors for PTB. Results: Among the 261 TB cases included, 46 patients (17.6%) had PTB, and 188 (72%) had EPTB. The percentage of female patients was significantly higher (P=0.003) in EPTB compared to PTB group. While the prevalence of diabetes mellitus (P=0.002), hypertension (P=0.017), coronary obstructive pulmonary disease (P=0.001), congestive heart failure (P=0.005), coronary artery disease (P=0.001) and immunosuppressive medication use (P=0.017) were significantly higher in PTB patients than in EPTB patients. Multivariate logistical analysis reveals that male (OR 2.6, 95% CI 1.3-5.5, P=0.009), diabetes mellitus (OR 2.7, 95% CI 1.2-6.1, P=0.015), and asthma (OR 6.3, 95% CI 1.2-33.9, P=0.032) were associated with an increased risk of PTB. Social security coverage (P

Objective: To evaluate the immunodiagnostic potential of crude Fasciola gigantica-worm (FWA) and egg antigen (FEA) in detecting anti-Schistosoma (S.) haematobium antibodies in sera and urine samples. Methods: This is a cross-sectional diagnostic study. Employing an indirect ELISA, antibodies against these antigens were assessed in samples from infected and non-infected individuals in both schistosomiasis endemic (NE) and non-endemic (NNE) areas, using microscopy as the diagnostic standard. Results: FWA-sera exhibited excellent diagnostic accuracy with an area under the curve (AUC) of 0.957, a sensitivity of 93.75%, and a specificity of 85.42% for discriminating between infected and non-infected individuals in non-endemic areas. FWA-urine also demonstrated robust performance, achieving AUC>0.95, sensitivity>97.0%, and specificity>85.0% in both NE and NNE categories. Notably, S. haematobium-specific antibody levels against FWA were significantly elevated in infected individuals in both endemic and non-endemic areas. FEA-sera exhibited outstanding diagnostic performance with sensitivity exceeding 90% and an AUC of 0.968 in non-endemic samples but not in FEA-urine. Conclusions: FWA-based ELISAs, applicable to both sera and urine, emerge as promising tools for S. haematobium diagnosis in resource-limited settings, offering advantages of high sensitivity and specificity with shared antigens with Fasciola. The superior diagnostic metrics of urine samples suggest their potential as a noninvasive biological sample for diagnostic purposes.

Objective: To determine the overall and pooled prevalence of Leishmania (L.) infantum in sandfly vectors in Iran. Methods: The present research conducted a systematic review and meta-analysis and searched regional databases such as PubMed, Scopus, Web of Science (WoS), Embase, PAHO Iris, LILACS, WHO Iris, and local databases named: SID, Magiran, Civilica, and also grey literatures. The current research included studies that were conducted in Iran and examined L. infantum in different sandfly vectors. The studies’ quality assessment/risk of bias assessment was evaluated by the Joanna Briggs Institute Critical Appraisal Checklist for prevalence data studies, and the data were analyzed by Stata 14 software. In addition, we examined 22 primary studies to estimate the overall prevalence of L. infantum among various vectors of visceral leishmaniasis. Results: According to the meta-analysis, the pooled prevalence of Phlebotomus (Ph.) tobbi, Ph. alexandri, Ph. kandelaki, Ph. perfiliewi, Ph. major, Ph. keshishiani were 5.34%, 4.36%, 2.23%, 1.79%, 4.37% and 1.18%. Ph. tobbi has the highest infection rate (25.00%) of L. infantum among the sandfly vectors. Conclusions: Visceral leishmaniasis is widespread in Fars, Ardebil, and East-Azerbaijan provinces, which are the most important endemic regions in Iran.

The rise of emerging infectious diseases has become notably prominent due to ecological changes and mutations in pathogens. The respiratory illness outbreak caused by the COVID-19 pandemic has spread globally. Natural products contain numerous structures and biological activities, offering ample options for discovering new antiviral drugs with unique targets and mechanisms. Andrographis paniculata has been utilized in Indian Ayurvedic, Swedish, Traditional Thai, and Chinese medicine to alleviate coughs, colds, and influenza symptoms. Early-stage laboratory studies indicate that this herbal extract may reduce inflammation and fever, and boost the body’s natural defenses against viruses, potentially leading to symptom relief. This review aims to systematically present clinical trial data about antiviral herbal formulations derived from Andrographis paniculata, delineating the antiviral effects of both natural and synthetic derivatives, along with in silico analyses.

Objective: To evaluate the cardioprotective effect of bioassay-guided isolated fractions of Cleome viscosa methanolic extract in streptozotocin-induced diabetic rats. Methods: Total phenolics, flavonoids, and in vitro antioxidant activities of the methanolic extract of Cleome viscosa were evaluated. The FD-40 fraction from this extract was further evaluated for antihyperglycemic efficacy (insulin and HbA1c), antioxidant activity, and cardioprotective effects (creatine kinase-MB, lactate dehydrogenase, and histopathology) in streptozotocin-induced diabetic rats. In silico studies were also conducted to assess the bioactivity of FD-40. Results: Cleome viscosa methanolic extract exhibited the highest antioxidant activity in DPPH, ABTS, H2O2, and FRAP assays compared to other extracts. Treatment with FD-40 (40 mg/kg b.w.) isolated from this extract normalized blood glucose, insulin, HbA1c, creatine kinase-MB, and lactate dehydrogenase levels in diabetic rats. It also significantly reduced oxidative stress by increasing antioxidant enzymes, decreasing lipid peroxidation as well as restoring the levels of ascorbic acid and glutathione. Histological study demonstrated that FD-40 treatment improved cardiac structure in diabetic rats. Molecular docking analysis revealed that phytocompounds from FD-40 had strong binding affinities with cardiac markers and oxidative enzymes. Hexose (5TMS) demonstrated greater binding affinity with xanthine oxidase and lactate dehydrogenase. Conclusions: FD-40 of Cleome viscosa methanolic extract exhibits significant cardioprotective effects in diabetic rats by regulating cardiac markers and reducing oxidative stress. The underlying mechanisms need to be elucidated in the future.

Objective: To elucidate the anti-melanogenic potential of Carex pumila Thunb. extract (FBCC-EP850). Methods: A collection of 180 plant extracts was tested for inhibition of mushroom tyrosinase activity using an in vitro assay. Among them, FBCC-EP850 exhibited the most promising inhibitory activity. Further analysis was conducted to investigate its mechanisms and therapeutic potential in reducing melanogenesis in B16F10 melanoma cells and zebrafish larvae. Results: FBCC-EP850 inhibited mushroom tyrosinase activity in a dose-dependent manner, with a half-maximal inhibitory concentration of 45.83 μg/mL. FBCC-EP850 at concentrations up to 50 pg/mL demonstrated minimal cytotoxicity against B16F10 melanoma cells and no adverse effects on zebrafish larvae. Treatment with 50 μg/mL of FBCC-EP850 significantly reduced α-melanocyte stimulating hormone-induced melanin production and suppressed cellular tyrosinase activity in B16F10 melanoma cells. Additionally, FBCC-EP850 at 25 and 50 μg/mL effectively diminished hyperpigmentation in α-melanocyte stimulating hormone-stimulated zebrafish larvae. Its anti-melanogenic action could be attributed to modulation of the cAMP-CREB-MITF signaling pathway. Conclusions: Carex pumila extract can inhibit melanogenesis by modulating the cAMP-CREB-MITF signaling pathway, which can be used as a promising candidate for treating hyperpigmentation disorders.

Objective: To evaluate the effect of Grifola frondosa polysaccharides (GFP) in a rat model of Alzheimer’s disease (AD). Methods: Seventy-five rats were divided into five groups: the normal control group and the AD group treated with or without GFP (100, 200, and 400 mg/kg). Behavioral responses in the open field test and elevated plus maze test were assessed. Additionally, the levels of malondialdehyde and ferric-reducing ability of plasma, and the mRNA expressions of TNF-α, IL-6, and IL-1β in the hippocampus were measured. Results: Treatment with GFP significantly improved AD-induced behavioral changes in the open field test and elevated plus maze test (P < 0.05). In addition, the level of malondialdehyde and the mRNA expressions of TNF-α, IL-6, and IL-1β were decreased by GFP treatment in a dose-dependent manner in AD rats (P < 0.05), while the level of ferric-reducing ability of plasma was significantly increased (P < 0.05). Conclusions: Oral administration of GFP can reduce inflammation and oxidative stress, as well as improve behavioral responses associated with AD, suggesting its potential use in AD treatment. However, additional studies are needed to elucidate its underlying mechanisms and efficacy.

Across the annals of time, organic molecules sourced from nature have found innumerable uses within the realms of healthcare, pharmaceuticals, and the study of living organisms. This abundant source of natural compounds has exhibited immense promise in the cure of diverse ailments, mainly neurodegenerative diseases owing to their minimum toxic and adverse effects. However, different challenges exist with phytocompounds from plants such as poor permeation, poor solubility (water/lipid), unsteadiness under extremely acidic pH conditions, and lack of targeting specificity. Furthermore, as a result of the existence of blood-brain barrier membrane and inconvenient pharmacokinetics characteristics of phytocompounds, their passage into the brain is constrained. In order to address this issue and augment the transportation of medications into the brain at a therapeutically effective level, it is imperative to formulate an innovative and pragmatic strategy. Many papers have shown that nanoformulations containing phytocompounds (resveratrol, quercetin, ferulic acid, curcumin, berberine, etc.) effectively improved many neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s diseases. This study provides an overview of phytocompounds that are used in nanosized lipid drug delivery systems. These systems are categorized according to lipid types and preparation techniques used in the formulation. Some studies regarding these systems and phytocompounds are also summarized.

Objective: To explore the effect of geraniol on cyclophosphamide- induced cardiotoxicity. Methods: Mice were divided into five groups: the control group, the cyclophosphamide group (200 mg/kg cyclophosphamide, i.p. on day 7), the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14, along with a single dose of cyclophosphamide on day 7, and the geraniol alone group (200 mg/kg geraniol from day 1 to day 14). At the end of the study, animals were sacrificed, and blood and heart were collected and analyzed for biochemical, histopathological, and immunohistochemical changes. Results: Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers, malondialdehyde, and inflammatory and apoptotic markers, while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity. Moreover, it remarkably alleviated histopathological aberrations in cardiac tissue. Conclusions: Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant, anti-inflammatory, and antiapoptotic effects.

Objective: To estimate the bone protective effect of alpinumisoflavone, a natural prenylated isoflavonoid, against glucocorticoid-induced osteoporosis in rats. Methods: Male Wistar rats received intramuscular administration of dexamethasone (4 mg/mL) at a dose level of 7 mg/kg for 5 weeks, and then alpinumisoflavone (5, 10, and 15 mg/kg) and alendronate (2 mg/kg) from 2 weeks. The body weight and organ weight (femoral, vagina, and uterus) were estimated. MicroCT analysis, bone turnover markers, bone parameters, oxidative stress parameters, and inflammatory cytokines were estimated. mRNA expressions of related genes were also estimated. Results: Alpinumisoflavone remarkably boosted body weight and organ weight (ureters and vagina), improved microCT analysis parameters, and boosted levels of bone markers. Besides, alpinumisoflavone considerably (P

Objective: To evaluate the anticancer potential of Cymbopogon citratus extract. Methods: GC-MS analysis was used to identify phytocomponents in the methanolic extract of Cymbopogon citratus. A fractionation method was employed to isolate and assess the bioactivity of different fractions and their cytotoxic activities against cancer cell lines HCT116, LoVo, Caco-2, and HT-29 were investigated. A dual staining method with acridine orange and ethidium bromide was used to assess the effect of the extract on cell apoptosis. Additionally, the expression levels of Bax and TP53 were quantified using realtime PCR in Caco-2 cells treated with the ethyl acetate fraction of Cymbopogon citratus extract. A protein array was employed to profile key pro- and anti-apoptotic proteins in Caco-2 cells. Moreover, molecular docking studies were conducted to investigate the interactions between key compounds of Cymbopogon citratus extract and specific apoptosis-related protein domains (PDB IDs: 7wql and 4bkx). Results: A significant growth inhibition was observed in Caco-2 cells treated with Cymbopogon citratus extract. Among the seven fractions of the plant extract, the ethyl acetate fraction showed the highest cytotoxicity against Caco-2 cells with an IC50 value of (6.16 ± 0.01) μg/mL. The immunofluorescence assay showed that the ethyl acetate fraction could induce apoptosis of Caco-2 cells. Moreover, the fraction upregulated the gene expressions of Bax and TP53 in a dose-dependent manner. The docking analysis demonstrated the interaction of five compounds isolated from the ethyl acetate fraction with key proteins in Caco-2 cells, indicating their anticancer properties. Conclusions: Cymbopogon citratus extract shows anticancer activity against Caco-2 cells by inducing apoptosis. It may be a promising candidate for the treatment of colon cancer, which needs further investigation.

Objective: To identify the clinical, laboratory, and radiological markers that could predict a positive GeneXpert result in patients suspected of tuberculous meningitis. Methods: In this prospective, observational study, patients with tuberculous meningitis were systematically evaluated. Various clinical, laboratory [including cerebrospinal fluid (CSF) microscopy, culture, and GeneXpert], and neuroimaging factors were examined. All participants were administered anti-tuberculous treatment and corticosteroids. A six-month follow-up was done to evaluate the outcome. Results: Of the 116 patients studied, 54 (46.6%) tested positive for GeneXpert, while 62 (53.4%) were negative. Third cranial nerve involvement (OR 3.71, 95% CI 1.052-13.09, P=0.04) and the presence of basal exudates on neuroimaging (OR 5.22, 95% CI 2.03-13.42, P=0.001) emerged as independent predictive factors for a positive GeneXpert result. A positive CSF GeneXpert result (P=0.002) and drug resistance (P=0.004) were significantly linked to adverse outcomes. Additionally, a high score on the Medical Research Council stage III (OR 5.64, 95% CI 1.18-26.87, P=0.03) and elevated CSF cell counts (OR 1.002, 95% CI 1.00-1.001, P=0.03) were identified as independent predictors of poor prognosis. Conclusions: Third cranial nerve involvement and the presence of basal exudates were significant indicators of a positive GeneXpert result. MRC stage III disability and elevated CSF cell counts predicted poor outcomes.

Tuberculosis caused by Mycobacterium (M.) tuberculosis remains a global public health threat. Over the last few decades, antitubercular research mainly focused on mechanisms of identifying by which activated macrophages can slaughter or the proliferation of M. tuberculosis bacilli prevented in a cell-dependent manner. In this regard, for disease resolution, inflammatory cytokines are very crucial. Here, we demonstrate how macrophages act as the first line of defense against the M. tuberculosis. Studies have revealed a dual role in M. tuberculosis infection played by macrophages. It is worth mentioning that the macrophages are the crucial immune effector and antigen-presenting cells that play the anti-tubercular response, which is the habitat of M. tuberculosis, hence, followed by progressing the disease protecting M. tuberculosis. This dual role can be correlated with the different macrophage polarization statuses, namely, M1 and M2. Herein, we have stated how the several polarization conditions of macrophages are directly linked to the immune responses during host and M. tuberculosis pathogen interactions. We have proposed that macrophage polarization and repolarization are of paramount significance for the anti-tubercular immune response that may involve a sterile cure of the disease. This article summarizes the immune response to M. tuberculosis, the polarization states of macrophages during M. tuberculosis and the repolarization of macrophages by some agents during some diseases including M. tuberculosis, which may be an important factor in the World Health Organization’s target to cure tuberculosis by 2035.

Objective: To elucidate the characteristics, management strategies, risk factors, and clinical impacts associated with adverse drug reactions (ADRs) induced by first-line antitubercular drugs to enhance tuberculosis (TB) management. Methods: A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak, Malaysia. Only the initial TB treatment and occurrence of specific ADRs within the study period were considered. Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs. Results: Among 2 953 cases, 705 (23.9%) developed ADRs. Cutaneous reactions were the most prevalent (47.1%), followed by hepatotoxicity (32.8%) and gastrointestinal disturbances (29.8%). Six out of seven types of ADRs investigated occurred within the intensive phase, mostly manifesting at approximately 2 weeks of initiation. Hepatotoxicity resulted in the majority (85.3%) of treatment discontinuations, while vision problems led to treatment modifications in half of the cases. Risk factors for all ADRs included age ≥60 years, females, illicit drug use, and comorbidities such as HIV-positive, diabetes, and chronic liver disease. Alcohol consumption was independently associated with hepatotoxicity. ADRs caused around one-third of interruptions exceeding 2 weeks (33.0%) and subsequently necessitated treatment restarts (34.5%). Conclusions: Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment. Close ADR monitoring and reporting are essential to strengthen ADR management.

Rationale: American tegumentary leishmaniasis comprises cutaneous and mucocutaneous manifestations caused by parasitic infections by various Leishmania species. This report details the clinical interventions for a patient with American tegumentary leishmaniasis in Mendoza, Argentina, a non-endemic region. Patient concerns: A 43-year-old male was admitted to a tertiary care hospital in Mendoza, Argentina Republic with a history of progressive nasal discharge, septal perforation, facial pain, and pruritus. Despite treatment for presumed nasal myiasis and vasculitis with granulomatosis, symptoms persisted. Diagnosis: American tegumentary leishmaniasis. Interventions: Intravenous liposomal amphotericin B. Outcomes: Follow-up at 30 days showed no recurrence of symptoms with a remarkable clinical improvement of the nasal lesion. Lessons: This case sheds light on the necessity of accurate identification for timely intervention and the need to recognize the diverse manifestations of American tegumentary leishmaniasis to avoid misdiagnosis.

Objective: To determine the current insecticide resistance status of Aedes (Ae.) aegypti and Ae. albopictus to four insecticides, namely 0.05% deltamethrin, 0.75% permethrin, 5% malathion and 0.25% pirimiphos–methyl using the World Health Organisation (WHO) susceptibility test kit. Methods: Adult bioassays were carried out using the standard protocol of the World Health Organisation. All F1 generation urban and suburban field strains of Ae. aegypti and Ae. albopictus were tested against pyrethroid and organophosphate insecticides, including the presence of piperonyl butoxide (PBO) in four replicates of 25 non-blood-fed female mosquitoes ranging from 3 to 5 days old. The Vector Control Research Unit (VCRU) laboratory strain served as a reference strain. Results: In this study, 0.05% deltamethrin demonstrated a lower value of knockdown time when 50% of the mosquito population died (KT50) and knockdown time when 95% of the mosquito population died (KT95), which is significantly more effective compared to 0.75% permethrin against adult female Ae. aegypti (urban and suburban) and Ae. albopictus (urban and suburban) (ANOVA, P

Objective: To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis (IPF) and to explore its underlying mechanisms using network pharmacology. Methods: IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin (5 mg/kg). Trigonelline was administered at doses of 25, 50, and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day. In IPF-induced mice, lung coefficient, immune cell infiltration in bronchoalveolar lavage fluid, and oxidative stress were measured. Histological alterations in lung tissues were also assessed. Moreover, network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF. Results: Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration, and mitigated physiological changes in the lung tissues of mice. Moreover, trigonelline alleviated bleomycin-induced histological alterations in lung tissues. Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets, such as NFKB1, HDAC2, HIF1A, and TLR4. Conclusions: The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF. It may be considered an antifibrotic agent for further clinical development.

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta (Aβ) aggregates, resulting from mutations in the amyloid precursor protein. The enzyme β-secretase, also known as β-site amyloid precursor protein cleaving enzyme 1 (BACE1), plays a crucial role in generating Aβ peptides. With no targeted therapy available for Alzheimer’s disease, inhibiting BACE1 aspartic protease has emerged as a primary treatment target. Since 1999, compounds demonstrating potential binding to the BACE1 receptor have advanced to human trials. Structural optimization of synthetically derived compounds, coupled with computational approaches, has offered valuable insights for developing highly selective leads with drug-like properties. This review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease agents. It summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status, indicating future directions for novel BACE1 inhibitors. The promising clinical results of Elenbecestat (E-2609) catalyze the development of effective, selective BACE1 inhibitors in the future.

Objective: To evaluate the effect of asiaticoside on streptozotocin (STZ) and nicotinamide (NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats. Methods: Asiaticoside (50 and 100 mg/kg body weight) was administered to STZ-NAD-induced diabetic rats for 45 days, and its effects on hyperglycaemic, carbohydrate metabolic, and insulin signaling pathway markers were examined. Results: Asiaticoside increased insulin production, lowered blood glucose levels, and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities. Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity. Furthermore, asiaticoside upregulated the mRNA expressions of IRS-1, IRS-2, and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal. Conclusions: Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis, gluconeogenesis, and insulin signaling pathways.

Objective: To evaluate anti-psoriatic activity of Coleus forskohlii in rats with imiquimod-induced psoriasis. Methods: Imiquimod was used to induce psoriasis in rats. Body weight, skin thickness, erythema, scaling, spleen weight, and histological alternations were measured to assess the effect of Coleus forskohlii. Furthermore, an emulgel formulation containing Coleus forskohlii 10% was prepared and characterized along with its ex vivo permeation studies. Results: The emulgel formulation containing Coleus forskohlii 10% had a pH of 5.40±0.36, with optimum spreadability of (31.67±2.08) g/(cms) and viscosity of (15 966.67±1 274.10) cps, and enhanced both the rate and the extent of drug permeation through psoriatic skin. In an ex vivo study, the quantity of drug permeated (19.18%), deposited (52.38%), and drug remaining in the donor compartments (28.31%) was satisfactory. Coleus forskohlii significantly alleviated imiquimod-induced psoriasis by increasing glutathione and superoxide dismutase activity, decreasing malondialdehyde and nitric oxide levels, and alleviating histological alternations in rat skin. Conclusions: Coleus forskohlii can alleviate imiquimod-induced psoriasis, which may be used as a therapeutic candidate for the treatment of psoriasis.

Objective: To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1 (SIRT1) signaling pathway. Methods: H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay. The protein expressions of SIRT1 and p38 MAPK were measured by Western blot. RT-qPCR was also used to determine S1RT1 mRNA expression. In addition, intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated. Results: Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability. It also increased SIRT1 and decreased p-p38 MAPK protein expressions. In addition, thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress, and enhanced antioxidant enzyme activities. However, silencing S1RT1 abrogated the protective effects of thrombopoietin, as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels. Conclusions: Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway. However, its protective effects need to be further verified in animal tests.

Objective: To investigate whether angiotensin II type 1 receptor (AGTR1 A1166C) gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension. Methods: This retrospective analysis included 198 patients (⩾18 years of age) who received valsartan monotherapy (80 mg/day) for newly developed essential hypertension at the authors’ center between January 1, 2020 and December 31, 2023. Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction (PCR)-melting curve analysis of genomic DNA from peripheral blood samples. A dominant genetic model for AGTR1 A1166C (AA genotype versus AC + CC genotype) was used. Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment (

Objective: To examine the socio-environmental factors associated with the assemblage of small mammals and the prevalence of Leptospira pathogen in poor suburban communities of Terengganu, Malaysia. Methods: We trapped small mammals from 119 trapping points scattered around three suburban communities of Terengganu using sausage-baited live traps. On the average, we set up five traps for three nights at each sampling point during the trapping period. Kidneys of captured animals were harvested and processed for Leptospira investigation. Additionally, environmental survey was conducted at each trapping point to obtain information about possible variables supporting small mammal assemblage. We used a generalized linear model to evaluate the effect of different socio-environmental variables on small mammals’ assemblage. Results: A total of 89 small mammals, specifically, Rattus norvegicus (n=39), Rattus rattus (n=27), Rattus exulans (n=10), Suncus murinus (n=11), and Tupaia glis (n=2) were captured from 1 385 trap nights. Fourteen individuals (15.7%) of the captured animals tested positive for Leptospira bacteria using PCR detection. Results of our generalized linear model showed only residences bordering vacant lots as the variable positively associated with small mammal occurrence in the three study sites. Conclusions: Small mammal community, especially the often neglected species, could harbour and potentially contribute towards pathogenic Leptospira maintenance in the study sites. To adequately control small mammals’ population and subsequent human zoonoses transmission, it is critical to advocate and promote appropriate infrastructure and suburban services, together with good hygiene practices that can reduce the animals’ access to food and harborage.

Objective: To evaluate the impact of the severe COVID-19 pandemic on neonates and develop strategies to improve their outcomes. Methods: We conducted an observational cross-sectional study at Children's Hospital 1 (CH1) from July 25, 2021, to May 31, 2022. All neonates who had fever or respiratory symptoms or were born from mothers with COVID-19 and had a positive RT-PCR SARS-CoV-2 result would be included. We classified neonates with COVID-19 into 2 groups: mild/moderate and severe for analysis. Differences between groups were analyzed using Fisher's exact test/Chi-square test for categorical variables and Student's t-test/Wilcoxon Rank Sum test for continuous variables. Results: This study included 88 newborns who had positive RT-PCR SARS-CoV-2 results. The severity COVID-19 rate among neonatal cases was found to be 13.6% (12/88), with a corresponding mortality rate of 1.1% (1/88). All severe cases showed lung abnormalities as evident on chest X-ray images. In addition to respiratory symptoms, a higher incidence of gastrointestinal manifestations, such as vomiting and diarrhea, was observed in the severe group, indicating a compelling association. The administration of anticoagulant and anti-inflammatory drugs in the study group resulted in a satisfactory outcome with no significant complications. Conclusions: The COVID-19 pandemic has had a substantial impact on the well-being of neonates. The management of COVID-19 in this population presents significant challenges.

Objective: To address the lack of research on invasive group B Streptococcus (GBS) infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals. Methods: Medical records from patients with GBS infection isolated from the sterile site, such as blood and cerebrospinal fluid from 14 July 2019 to 15 December 2020, were reviewed from six major hospitals in Peninsular Malaysia. Inclusion criteria were invasive GBS, sterile sites and non-repeated GBS isolated from the same patients in the same admission. Viable isolates were re-identified for GBS and serotyped. Results: A total of 118 patients were eligible, with a majority of non-pregnant adults (76.3%). Over half of the patients (62.7%) had underlying medical conditions, with diabetes as the most common disease, followed by respiratory disease, renal disease, cardiovascular disease and skin and soft tissue disease. The most common manifestations were sepsis, followed by soft tissue abscess, diabetic foot ulcer, wet gangrene and cellulitis. The overall mortality was 7.6%. The most common serotype was serotype V. Conclusions: Invasive GBS infection among non-pregnant adults showed a rising trend, particularly among diabetic individuals. The study underscores the importance of reducing risk factors and highlights the necessity of developing GBS vaccination as a preventive strategy for both infants and adults.

Rationale: Vanishing lung syndrome is rare and can be associated with a history of smoking and marijuana use. The occurrence of giant bullae can also be linked to infections, particularly tuberculosis in tropical countries. Patient concerns: A 26-year-old male complained of weakness, severe vomiting, and reduced breathlessness when lying on the left side. He had a history of pulmonary tuberculosis two years ago. Diagnosis: Symptomatic bradycardia in tuberculosis-related giant bullae. Interventions: The patient was recommended to undergo an elective bullectomy, but he decided not to proceed with the procedure. Atropine sulfate was administered to alleviate symptoms of bradycardia, while a standardized anti-tuberculosis regimen were started for the next six months. Outcomes: Following 7 days of intensive care treatment involving antituberculosis medications and atropine sulfate, the patient achieved hemodynamic stability, opting against bullectomy despite residual symptoms of dyspnea. Subsequent six months of antituberculosis therapy notably alleviated symptoms without requiring bullectomy. Lessons: Increasing intrathoracic pressure can also be caused mechanically by giant bullae. Cardiac symptoms in vanishing lung syndrome are reversible and can be alleviated once the underlying cause is addressed. In this case, symptomatic bradycardia was reduced only with tuberculosis treatment without bullectomy intervention.

Objective: To determine the risk factors for hypertension in pregnant women, which is a significant cause of maternal and newborn morbidity and mortality in Indonesia. Methods: This was a cross-sectional study used secondary data from the 2018 Indonesian Basic Health Research. Pregnant women aged 15-54 years in the second and third trimesters were eligible. The history of hypertension in pregnant women was the dependent variable. The independent variables consisted of the demographic characteristics of pregnant women including pregnancy age, gestational age, education, occupation, place of residence, and region of residence. This study used multivariate logistic regression to determine the risk factors for hypertension in pregnant women in Indonesia. Results: Among 6479 respondents included in this study, 11 (7.0%) had a history of diabetes mellitus (DM) and hypertension compared to pregnant women who did not have a history of DM (0.1%). The dominant risk factors for hypertension in pregnant women in Indonesia include maternal age above 35 years (OR 3.67, 95% CI 2.54-5.32), third-trimester pregnancy (OR 2.40, 95% CI 1.72-3.35), primigravida (OR 1.78, 95% CI 1.19-2.68), excessive consumption of salty foods (OR 1.44, 95% CI 1.03-2.03), and diabetes mellitus (OR 10.20, 95% CI 3.04-32.23). Conclusions: Great efforts must be made to increase public awareness about the dangers of hypertension in pregnant women through early diagnosis and treatment, education on sodium intake, and appropriate care for pregnant women with DM.

Rationale: Nocardia is a soil saprophyte, which can cause disseminated infection in immunocompromised patients. Early diagnosis and treatment can greatly improve prognosis. Patient concern: A 26-year-old male presented with repeated episodes of fever, cough and breathlessness for 3 months. Diagnosis: Mixed infection of Nocardia (N.) farcinica and N. cyriacigeorgica with diabetes and Cushing’s syndrome. Interventions: N. cyriacigeorgica was isolated from empyema fluid and N. farcinica from blood. Based on antimicrobial susceptibility, he was treated with imipenem, cotrimoxazole and amikacin. Outcome: Patient expired due to infection and delayed diagnosis. Lesson: Several cases of infection due to N. farcinica or N. cyriacigeorgica have been reported. But mixed infection caused by these two species is rare. Pulmonary and disseminated nocardiosis is associated with high mortality, especially in immunocompromised hosts. So early diagnosis and prompt treatment is needed.