Biological Activities of Sesquiterpenoids： A Review / 中国实验方剂学杂志

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

Exploring effects of atmospheric conditions in hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations. Individuals with HHT often identify low humidity and temperature as detrimental to epistaxis severity. We set out to assess the relationship between humidity and temperature on epistaxis severity in patients with HHT. METHODS: Retrospective cross-sectional study at an academic hospital with an HHT center between July 1, 2014 and January 1, 2022. The primary outcome of this study was ESS. Pearson correlation analyses and multiple linear regression analyses were performed to test the association between weather variables and epistaxis severity scre (ESS). Results were reported as coefficient and 95% confidence interval (CI). RESULTS: Four hundred twenty-nine patients were included in the analysis. Through a Pearson correlation analysis, neither humidity (regression coefficient = -0.01; 95% CI, -0.006 to 0.003; p = 0.50), daily low temperature (regression coefficient = 0.01; 95% CI, -0.011 to 0.016; p = 0.72), or daily high temperature (regression coefficient = 0.01; 95% CI, -0.004 to 0.013; p = 0.32) were significantly correlated with ESS. In a multiple linear regression analysis, adjusting for both daily low temperature and humidity, medications taken, demographics, and genotype, neither daily low temperature (regression coefficient = -0.02; 95% CI, -0.04 to 0.01; p = 0.14) nor humidity (regression coefficient = 0.01; 95% CI, -0.01 to 0.01; p = 0.64) were significantly associated with ESS. CONCLUSION: We have shown in a large clinical sample that neither humidity nor temperature were strongly correlated with HHT patient epistaxis severity.

Identifying racial disparities in hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis (nose bleeds), mucosal telangiectasias (spider veins), and arteriovenous malformations. Although HHT affects all racial groups, few studies have explored racial disparities among patients with HHT. METHODS: We performed a retrospective chart review of HHT patients who were seen at a single academic center between July 1, 2014 and January 1, 2022. The primary outcomes of this study were the Epistaxis Severity Score (ESS) and the presence of pulmonary, cerebral, gastrointestinal, spinal, and hepatic arteriovenous malformations (AVMs). We analyzed racial differences using t-tests and analysis of variance (ANOVA) for continuous variables, and chi-squared tests for categorical variables. We then performed multivariable linear and logistic regressions on outcomes. RESULTS: Our review identified 35 Asian, 6 Black or African American, 72 Hispanic or Latino, and 244 White or Caucasian patients who met the inclusion criteria. Through an analysis of variance model, race/ethnicity was not significantly associated with ESS. Two univariable logistic regression models between race and both pulmonary and brain AVMs showed that race was associated with the incidence of pulmonary AVMs (p<0.01), with Asian patients at a 2.3-fold increased risk of pulmonary AVMs compared with White patients (p=0.03). Race was also associated with the incidence of cerebral AVMs (p<0.01) with Hispanic or Latino patients at a 4.8-fold increased risk compared with White patients (p<0.01). CONCLUSION: Patients who identified as Asian may have higher rates of pulmonary AVMs while patients identifying as Hispanic or Latino may have more cerebral AVMs. The correlations may be important for identifying risk factors in certain patient populations.

Pulmonary Aspergilloma in a Young Immunocompetent Female: A Rare Clinical Dilemma.

Depending on the host's immunological and respiratory systems, Aspergillus can induce infectious and allergic diseases. Most of the spread occurs in immunocompromised people, whereas aggressive disorder in immunocompetent patients is unusual. We report the case of a 19-year-old female who had shortness of breath, right-sided chest discomfort, and intermittent hemoptysis for six months before being diagnosed with pulmonary aspergilloma. The initial chest x-ray revealed a massive right pneumothorax and a 7.2 cm rounded opacity in the right lower lung. A subsequent computed tomography (CT) chest with contrast revealed a 6.7 cm cavitating mass occupying the right lower lobe. An open right thoracotomy and right lower lobectomy showed a cavitary fungus ball with septate branching hyphae and subsequent methenamine silver staining consistent with Aspergillus in conjunction with a positive Aspergillus antigen. We strongly suggest that pulmonary aspergillosis should be suspected regardless of age or immunocompetence in patients with prolonged cough, hemoptysis, unilateral chest discomfort, and pneumothorax.

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention.

Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.

Frequency of Celiac Disease in Patients With Chronic Diarrhea.

INTRODUCTION: Celiac disease (CD) is an immune-mediated disease caused by ingesting gluten-containing foods and is characterized mainly by malabsorptive diarrhea. Furthermore, distinguishing between mild disease and asymptomatic individuals is critical and necessitates a high level of clinical suspicion. Short stature, delayed puberty, bone abnormalities, neurological problems, and intestinal cancer can all be consequences of a delayed diagnosis. This study aimed to determine the prevalence of celiac disease among our community's recurrent diarrhea patients. METHODS: This was a cross-sectional study aimed at determining the frequency of celiac disease in patients with chronic diarrhea. One hundred eighty-eight patients between the ages of 18 and 60 years who had chronic diarrhea lasting greater than three months were enrolled in this study. Stratification was utilized to control for modifiers. A p-value of ≤ 0.05 was considered significant. RESULTS: A total of 74.5% of patients (n=140) were male, while 25.5% (n=48) were female with a mean age of 38.48±10.85 years. The average duration of celiac disease symptoms was 8.17± 3.75 months. Celiac disease was found in 12.2% (n=23) of the individuals. Also, 21% of individuals with a positive family history of CD devolved CD, compared to those without prior CD family history (p=0.01). CONCLUSIONS: In individuals with chronic diarrhea for more than three months, the prevalence of celiac disease was determined to be 12.2% (n=23). There was a statistically significant difference between those with a positive family history of CD and those who did not have the condition.

Regulation of Hedgehog Signaling by miRNAs and Nanoformulations: A Possible Therapeutic Solution for Colorectal Cancer.

Hedgehog (Hh) signaling aberrations trigger differentiation and proliferation in colorectal cancer (CRC). However, the current approaches which inhibit this vital cellular pathway provoke some side effects. Therefore, it is necessary to look for new therapeutic options. MicroRNAs are small molecules that modulate expression of the target genes and can be utilized as a potential therapeutic option for CRC. On the other hand, nanoformulations have been implemented in the treatment of plethora of diseases. Owing to their excessive bioavailability, limited cytotoxicity and high specificity, nanoparticles may be considered as an alternative drug delivery platform for the Hh signaling mediated CRC. This article reviews the Hh signaling and its involvement in CRC with focus on miRNAs, nanoformulations as potential diagnostic/prognostic and therapeutics for CRC.

MicroRNAs and Natural Compounds Mediated Regulation of TGF Signaling in Prostate Cancer.

Prostate cancer (PCa) is with rising incidence in male population globally. It is a complex anomaly orchestrated by a plethora of cellular processes. Transforming growth factor-beta (TGF-ß) signaling is one of the key signaling pathways involved in the tumorigenesis of PCa. TGF-ß signaling has a dual role in the PCa, making it difficult to find a suitable therapeutic option. MicroRNAs (miRNAs) mediated regulation of TGF-ß signaling is responsible for the TGF-ß paradox. These are small molecules that modulate the expression of target genes and regulate cancer progression. Thus, miRNAs interaction with different signaling cascades is of great attention for devising new diagnostic and therapeutic options for PCa. Natural compounds have been extensively studied due to their high efficacy and low cytotoxicity. Here, we discuss the involvement of TGF-ß signaling in PCa with the interplay between miRNAs and TGF-ß signaling and also review the role of natural compounds for the development of new therapeutics for PCa.

Contrast-induced Acute Kidney Injury in Patients with Liver Cirrhosis: A Retrospective Analysis.

Contrast-induced acute kidney injury (CI-AKI) has been studied less extensively in patients with liver cirrhosis (LC). It is unclear whether the presence of severe liver disease is actually a predisposing factor for CI-AKI. Liver cirrhosis is extremely common in Pakistan and is attributed to the high prevalence of chronic viral hepatitis. Patients with LC often undergo contrast-enhanced computed tomograms (CECT) for various diagnostic and therapeutic purposes, and there have been concerns regarding them being at risk for CI-AKI. The available literature on this topic is scanty, and no study has been conducted in Pakistan. The purpose of this study, therefore, was to determine the frequency of CI-AKI in patients with LC undergoing CECT and to determine any significant predispositions. We retrospectively analyzed the records of 470 LC patients at our center. The frequency of CI-AKI in our study was 5.1%. A higher mean model for end-stage liver disease (MELD), MELD including sodium (MELD-Na), and Child-Pugh (CP) scores was significantly associated with developing CI-AKI (p<0.05). Patients with CI-AKI also had a significantly higher mean international normalized ratio (INR) and serum bilirubin levels, with lower mean venous bicarbonate and serum sodium levels (p<0.05). Our results show that patients with a more advanced liver disease and poorer synthetic function are increasingly susceptible to developing CI-AKI. Further studies can investigate the role of bicarbonate therapy in preventing CI-AKI in LC.

Association of Hemodialysis Inadequacy and Duration with Restless Legs Syndrome: A Cross-sectional Study.

Restless legs syndrome (RLS) is a common neurological disorder in hemodialysis (HD) patients. It is associated with poor sleep and decreased quality of life. The precipitants for the disorder are still poorly understood. The condition has not been studied extensively in Pakistan, which has a vast majority of end-stage renal disease patients on maintenance HD. We aimed to determine the prevalence of this condition in patients attending HD units of the largest renal dialysis center in Northern Pakistan. We also strived to determine any associations with dialysis inadequacy and the total duration of HD. This was an observational study comprising 279 patients. RLS was diagnosed using the International Restless Leg Syndrome Study Group criteria. Dialysis adequacy was determined using the Urea Reduction Ratio and the Kt/V technique. The prevalence of RLS in this large HD population was 24%. Our results show that a longer duration and greater number of HD sessions were significantly associated with the development of RLS (p<0.05). Dialysis inadequacy was not associated with the development of the disorder. These results may indicate that the pro-inflammatory nature of hemodialysis may have a role in the pathophysiology of RLS in HD patients and prolonged exposure to it may make them more prone to developing the disorder.

Central Diabetes Insipidus and Hyperglycemic Hyperosmolar State Following Accidental Carbon Monoxide Poisoning.

Carbon monoxide poisoning is common and carries significant morbidity and mortality. The nervous system, particularly the brain, is frequently affected by it, owing to its high metabolic activity and oxygen requirements. Carbon monoxide damages the nervous system by both hypoxic and inflammatory mechanisms. Central diabetes insipidus is an extremely rare complication of carbon monoxide poisoning. Herein, we report the case of a young lady, who developed this complication and severe hypernatremia after accidental carbon monoxide poisoning. She also developed a hyperglycemic hyperosmolar state during the treatment for hypernatremia. To the best of our knowledge, both these entities have not been reported together in association with carbon monoxide poisoning. The purpose of this article is to emphasize the anticipation and early recognition of central diabetes insipidus in carbon monoxide poisoning. This can prevent severe hypernatremia and complications associated with its presence and treatment.

Sporadic actinomycosis of the hip complicated by Central Nervous System infection.

Actinomycosis is caused by the Gram positive filamentous Actinomyces bacterial species that are normal commensals of the oral cavity. Due to their low virulence, disease is rare in the immune competent patient. Although it may afflict any system in the body, involvement of the musculoskeletal system is uncommon. Here in, we describe the case of a 60 year old lady presenting with low grade fever, left hip pain and drowsiness. She was diagnosed as left hip actinomycosis on Computed tomogram (CT) guided biopsy and histopathological analysis of infiltrative lesions identified on Magnetic Resonance Imaging (MRI). She also had meningitis diagnosed on cerebrospinal fluid analysis which improved with treatment of actinomycosis. Actinomycosis of the hip is rare, and occurs in the presence of described predisposing factors. To the best of our knowledge, this is the first case of sporadic actinomycosis of the hip complicated by meningitis in an immune competent individual.

Severe acute respiratory distress syndrome secondary to Plasmodium vivax malaria.

Plasmodium Vivax malaria is generally considered as a benign self-limiting illness and is less often associated with more severe disease and complications. Amongst these, acute respiratory distress syndrome (ARDS) is a particularly rare complication. The few cases reported describe the onset of ARDS after initiation of anti-malarial therapy as a post inflammatory response. Here we report the case of a 45 year old male who was a victim of severe Plasmodium vivax malaria culminating into ARDS, prior to the initiation of anti-malarial therapy. He was treated with invasive ventilation and anti-malarial therapy and made a complete and uneventful recovery.

Acute Abdominal Aorta Thrombosis and Ischemic Rhabdomyolysis Secondary to Severe Alcohol Intoxication.

Acute alcohol intoxication is a common cause of emergency visits worldwide. Although moderate alcohol consumption is protective against coronary artery disease, binge drinking is associated with adverse cardiovascular and neurological outcomes and may even cause sudden death. Although, few past accounts of venous thrombosis with alcohol binge drinking are available, arterial thrombosis with the condition has never been reported in the literature. We present the unusual case of a young Afghan male, who presented to us with painful, tender and swollen legs three days after a heavy alcohol binge on a Saturday night. He was diagnosed as a case of acute limb ischemia secondary to massive abdominal aorta and bilateral femoral artery thrombosis. He also had acute renal failure secondary to rhabdomyolysis. Cardiac workup revealed new onset paroxysmal atrial fibrillation and a large thrombus in the left ventricular cavity. His blood ethanol level was high. He was treated by a multidisciplinary team; urgent surgical thrombectomy for thrombotic complications, intravenous fluid hydration and later renal replacement therapy for acute renal failure. To the best of our knowledge, such a constellation of clinical features in association with severe acute alcohol intoxication has not been reported in the literature. We believe, the procoagulant nature of high blood ethanol levels and the onset of atrial fibrillation after the heavy alcohol binge, known as the holiday heart syndrome, precipitated the thrombotic events leading to rhabdomyolysis and acute renal failure. Through this case, we conclude that a very heavy alcohol binge may cause thrombotic occlusion of the abdominal aorta and femoral arteries resulting in ischemic rhabdomyolysis and acute renal failure. A high index of suspicion must be kept, especially for a patient presenting with tender, swollen lower limbs and acute renal failure after an alcohol binge.

Molecular Distribution of Deafness Loci in Various Ethnic Groups of the Punjab, Pakistan.

OBJECTIVE: To determine the existence of autosomal recessive deafness loci in different ethnic tribes of the Punjab. STUDY DESIGN: Descriptive observational study. PLACE AND DURATION OF STUDY: Department of Human Genetics and Centre of Excellence in Molecular Biology, University of Health Sciences, Lahore, from July 2009 to March 2012. METHODOLOGY: Healthy willing subjects with autosomal recessive deafness loci were studied for selected deafness loci. Those who were unhealthy and gave history of infectious disease were excluded. DNAextraction was carried out using the inorganic method. Fluorescently labeled microsatellite markers were used for amplification of desired regions by PCR (Polymerase Chain Reaction). Automated allele assignment was performed using the ABI PRISM GeneScan Analysis Software Version 3.7 for Windows NTPlatform. Two-point LOD scores were calculated using the FASTLINK computer package (Schaffer 1996) and MLINK was used for calculation and 95% CI (confidence intervals) were calculated. RESULTS: One hundred and thirty two individuals of 8 families were analyzed. Three families (SAPun-03, SAPun-10 and SAPun-15) were found linked to DFNB12; two families (SAPun-05 and SAPun-17) were found linked to DFNB8/10, while three families (SAPun-06, SAPun-13 and SAPun-19) were found linked to DFNB29, DFNB36 and DFNB37 respectively. CONCLUSION: The genotyping results revealed that DFNB12 locus was the most common followed by DFNB8/10 locus, while the Loci DFNB29, DFNB36 and DFNB37 were less common.