The relationship between academic stress and depression among college students during the COVID-19 pandemic: a cross-sectional study from China.

BACKGROUND: The COVID-19 pandemic is a global public health crisis. During the COVID-19 pandemic, mental health has attracted great attention. However, there is a lack of research on the relationship between academic stress and depression in Chinese college students and its mechanisms. Therefore, this study investigated the mechanisms of coping style, sleep quality, and interpersonal relationship in academic stress and depression among college students. METHODS: The cross-sectional study was conducted from May to June 2022 through face-to-face questionnaires with college students in Anhui Province, China. The questionnaires included sociodemographic information, the Simplified Coping Style Questionnaire, and the Self-Rating Depression Scale. Ordered logistic regression model was used to study the relationship between academic stress and depression of college students during the COVID-19 pandemic through the mechanism analysis of coping style, sleep quality and interpersonal relationship. RESULTS: Two thousand thirty-three Chinese college students participated in the study, including 1,285 female and 748 male college students, with an average age 19.81 years old (SD = 1.22 years old). The results showed that (1) Academic stress had a significant impact on depression in college students under the background of COVID-19 (p < 0.01); (2) The influence of academic stress on depression had a difference in work experience as student cadres, which showed that college students who had served as student cadres were less affected by academic stress (p < 0.10), college students who had not served as student cadres were greatly affected by the academic stress (p < 0.05); (3) College students' attitudes toward COVID-19 significantly affected depression (p < 0.01); (4) Counselors' concern had a significant impact on college students' depression (p < 0.01); (5) Positive coping style, high quality sleep and good interpersonal relationship were the important mechanisms of the impact of academic stress on college students' depression. CONCLUSIONS: This study provides new findings for in-depth understanding of the relationship between academic stress and depression among college students in China during the COVID-19 pandemic, which is conducive to the provision of targeted intervention measures for the mental health of college students.

Semi-rational engineering an aldo-keto reductase for stereocomplementary reduction of α-keto amide compounds.

Enantio-pure α-hydroxy amides are valuable intermediates for the synthesis of chiral pharmaceuticals. The asymmetric reduction of α-keto amides to generate chiral α-hydroxy amides is a difficult and challenging task in biocatalysis. In this study, iolS, an aldo-keto reductase from Bacillus subtilis 168 was exhibited as a potential biocatalyst, which could catalyze the reduction of diaryl α-keto amide such as 2-oxo-N, 2-diphenyl-acetamide (ONDPA) with moderate S-selectivity (76.1%, ee) and 60.5% conversion. Through semi-rational engineering, two stereocomplementary variants (I57F/F126L and N21A/F126A) were obtained with ee value of 97.6% (S) and 99.9% (R) toward ONDPA (1a), respectively, delivering chiral α-hydroxy amide with > 98% conversions. Moreover, the excellent S- and R-preference variants displayed improved stereoselectivities toward the other α-keto amide compounds. Molecular dynamic and docking analysis revealed that the two key residues at 21 and 126 were identified as the "switch", which specifically controlled the stereopreference of iolS by regulating the shape of substrate binding pocket as well as the substrate orientation. Our results offer an effective strategy to obtain α-hydroxy amides with high optical purity and provide structural insights into altering the stereoselectivity of AKRs.

The impact of family functioning on depression in college students: A moderated mediation model.

BACKGROUND: The depression of college students is increasing. Family dysfunction is a potential risk factor for depression. More research is needed to uncover the relationship and influencing mechanism. Based on this, this study examined the mediating effect of coping style and the moderating effect of gender in family functioning and depression among college students. METHODS: From May to June 2022, a cross-sectional survey was conducted among 2033 college students (16-24 years old) from universities in Anhui Province, China, including 1285 females (63.21 %) and 748 males (36.79 %), with an average age of 19.81 years old (SD = 1.22 years old). There were 651 (32.02 %) only child. Family functioning was assessed by Family Assessment Device, coping style was assessed by Simplified Coping Style Questionnaire and depression was assessed by Self-rating Depression Scale. Common method bias was performed by Harman's single-factor test. Mediating effect was analyzed by stepwise regression. Moderating effect was analyzed by moderated multiple regression. RESULTS: There was no serious common method bias in this study. Good family functioning had a negative predictive effect on depression in college students (r = -0.56, p < 0.001). Coping style partially mediated the predictive effect of family functioning on depression, and the mediating effect accounted for 33.73 % of the total effect. The interaction term of family functioning and gender was significant predictor of coping style (ß = 0.33, t = 2.69, p < 0.05) and depression (ß = -1.98, t = -2.46, p < 0.05). CONCLUSIONS: Good family functioning is a negative predictor of depression in college students. Coping style plays a partial mediating role between family functioning and depression. The first half path and the direct path of the mediation model are modulated by gender.

Non-pharmacological and drug treatment of autonomic dysfunction in multiple system atrophy: current status and future directions.

Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. Early onset and extensive autonomic dysfunction, including cardiovascular dysfunction characterized by orthostatic hypotension (OH) and supine hypertension, urinary dysfunction characterized by overactive bladder and incomplete bladder emptying, sexual dysfunction characterized by sexual desire deficiency and erectile dysfunction, and gastrointestinal dysfunction characterized by delayed gastric emptying and constipation, are the main features of MSA. Autonomic dysfunction greatly reduces quality of life and increases mortality. Therefore, early diagnosis and intervention are urgently needed to benefit MSA patients. In this review, we aim to discuss the systematic treatment of autonomic dysfunction in MSA, and focus on the current methods, starting from non-pharmacological methods, such as patient education, psychotherapy, diet change, surgery, and neuromodulation, to various drug treatments targeting autonomic nerve and its projection fibers. In addition, we also draw attention to the interactions among various treatments, and introduce novel methods proposed in recent years, such as gene therapy, stem cell therapy, and neural prosthesis implantation. Furthermore, we elaborate on the specific targets and mechanisms of action of various drugs. We would like to call for large-scale research to determine the efficacy of these methods in the future. Finally, we point out that studies on the pathogenesis of MSA and pathophysiological mechanisms of various autonomic dysfunction would also contribute to the development of new promising treatments and concepts.

[Application of acupuncture in inhibiting intestinal peristalsis in colonoscopy].

Acupuncture regulating gastrointestinal motility has the characteristics of bidirectional benign regulation, acupoint specificity and immediacy. And its regulation is mainly achieved through the "neuro-endocrine-immune" network system. Acupuncture at Neiguan (PC 6) and Hegu (LI 4) to inhibit intestinal peristalsis may have good application value in colonoscopy.

Suppression effect and safety of acupuncture on colonic spasm during colonoscopy: a randomized controlled trial.

Background: Intestinal spasm and peristalsis during colonoscopy are common but undesirable phenomena, which can easily lead to a missed diagnosis of colorectal polyps and other diseases, and antispasmodic drugs can have adverse side effects. Previous studies find that acupuncture can regulate abnormal gastrointestinal motility. But evidence quality is low and limited at present, and high-quality studies are required. So this study sought to explore the efficacy and safety of acupuncture in inhibiting colonic spasm during endoscopy. Methods: In this prospective, single-blinded, randomized controlled trial, 54 patients experiencing intestinal spasms during colonoscopy were randomly assigned to receive either acupuncture of the bilateral Hegu (LI 4) and Neiguan (PC 6) points (n=27) or sham acupuncture (n=27). The sham points were located 1 cm above the proximal end of the true points and had no known function. The primary outcome was the latency time to colonic spasm suppression, and the secondary outcomes were the duration of colonic spasm suppression, the proportion of patients with rebound spasms within 5 minutes, and adverse events related to acupuncture-related side effects. Results: A total of 54 patients were eligible, and 27 in each group. There was no significant difference in the background characteristics of the patients in the 2 groups. The latency time to spasm suppression of the treatment group was significantly shorter than that of the sham control group (acupuncture: 32.00 s vs. sham: 82.00 s; P<0.001). However, the duration of colonic spasm suppression was similar (acupuncture: 300 s vs. sham: 268 s; P=0.142). No rebound spasms were observed in the treatment group but rebound spasms were observed in 3 patients in the sham control group (acupuncture: 0% vs. sham: 11.1%; P=0.236). No adverse events were observed in either group. Conclusions: Acupuncture of the bilateral Hegu (LI 4) and Neiguan (PC 6) points can shorten the latency time to spasm suppression, and may be used to suppress colonic spasm during colonoscopy. Trial registration: Chinese Clinical Trial Registry ChiCTR2000037796.

Physiological parameters and differential expression analysis of N-phenyl-N'-[6-(2-chlorobenzothiazol)-yl] urea-induced callus of Eucalyptus urophylla × Eucalyptus grandis.

In this study, we analyzed differences in the enzyme activities and transcriptomes of embryogenic and non-embryogenic calli to gain insights for improving the success of tissue culture-based breeding. A total of 2,856 differentially expressed genes (DEGs; 1,632 up-regulated and 1,224 down-regulated) were identified based on RNA sequencing and verified by reverse transcription quantitative polymerase chain reaction. Gene set enrichment analysis revealed that many of the up-regulated DEGs in embryogenic callus were enriched in the photosynthesis processes. Furthermore, the enzyme activity, hormone content, and cytokinin oxidase/dehydrogenase (CKX) gene expression analyses were found to be consistent with the transcriptome results. Cytokinin biosynthesis in N-phenyl-N'-[6-(2-chlorobenzothiazol)-yl] urea (PBU)-induced embryogenic callus increased owing to CKX repression. Measurement of endogenous hormones by high-performance liquid chromatography revealed that, compared with non-embryogenic callus, in embryogenic callus, the indole-3-acetic acid, abscisic acid and trans-zeatin riboside content had significantly higher values of 129.7, 127.8 and 78.9 ng/g, respectively. Collectively, the findings of this study will provide a foundation for elucidating the molecular mechanisms underlying embryogenic callus differentiation and can potentially contribute to developing procedures aimed at enhancing the success of callus-based plant regeneration.

Characterization and evaluation of a peptide-based siRNA delivery system in vitro.

Since its inception more than a decade ago, gene silencing mediated by double-stranded small interfering RNA (siRNA) has been widely investigated as a potential therapeutic approach for a variety of diseases. However, the use of siRNA is hampered by its rapid degradation and poor cellular uptake in vitro and in vivo. Recently, peptide-based carriers have been applied to siRNA delivery, as an alternative to the traditional delivery systems. Here, a histidine-containing amphipathic amino acid pairing peptide, C6M3, which can form complexes with siRNA, was used as a new siRNA delivery system. This peptide exhibited a high affinity for siRNA and ability to efficiently deliver siRNA into the cells. The interaction of C6M3 with siRNA was investigated to determine the loading capacity of C6M3 at different peptide/siRNA molar ratios. At C6M3/siRNA molar ratio of 10/1, siRNA molecules were entirely associated with C6M3 as indicated by a gel electrophoretic assay and further confirmed by zeta potential analysis. The particle size distribution of the C6M3-siRNA complexes was studied using dynamic light scattering, which showed an intensity-based size distribution peaked approximately at 100 nm in RNase-free water and 220 nm in the Opti-MEM medium. C6M3 adopted a helical secondary structure in RNase-free water and became more so after forming complexes with siRNA. The interaction of siRNA with C6M3 is an entropy-driven spontaneous process, as determined by isothermal titration calorimetry (ITC) study. The efficiency of cellular uptake of the siRNA complexes at different C6M3/siRNA molar ratios was evaluated, and the results showed that C6M3 promoted efficient cellular uptake of siRNA into cells. Furthermore, a significant level of GAPDH gene silencing efficiency (69%) was achieved in CHO-K1 cells, with minimal cytotoxicity.

DEGylation Enhanced the Stability of Peptide-siRNA Complexes in Serum.

Small interfering RNA (siRNA) shows great therapeutic potential due to its ability to regulate gene expression in a highly selective manner, but this application has been limited by effective delivery, partly because of the low nuclease resistance of siRNA in the presence of serum, and inefficient cellular uptake. We previously reported a library of cell-penetrating and amino acid-pairing peptides that facilitate effective siRNA delivery to mammalian cells without causing cytotoxicity, but they are unstable within serum-containing medium. Here, we investigated the possibility of conjugating the peptide with diethylene glycol to improve its serum stability without compromising its gene-regulation capability. One of the most promising peptides, C6M1, was conjugated with diethylene glycol, and its incorporated siRNA complexes had excellent serum stability and highly efficient cellular uptake with negligible cytotoxicity. The gene-silencing ability of diethylene glycol conjugated-peptide/siRNA complexes was comparable to that of non-conjugated peptide/siRNA at both mRNA and protein levels. Our data demonstrate that conjugating peptides with diethylene glycol is a promising method for improving siRNA delivery by improving its serum stability.

Bacterial Acclimation Inside an Aqueous Battery.

Specific environmental stresses may lead to induced genomic instability in bacteria, generating beneficial mutants and potentially accelerating the breeding of industrial microorganisms. The environmental stresses inside the aqueous battery may be derived from such conditions as ion shuttle, pH gradient, free radical reaction and electric field. In most industrial and medical applications, electric fields and direct currents are used to kill bacteria and yeast. However, the present study focused on increasing bacterial survival inside an operating battery. Using a bacterial acclimation strategy, both Escherichia coli and Bacillus subtilis were acclimated for 10 battery operation cycles and survived in the battery for over 3 days. The acclimated bacteria changed in cell shape, growth rate and colony color. Further analysis indicated that electrolyte concentration could be one of the major factors determining bacterial survival inside an aqueous battery. The acclimation process significantly improved the viability of both bacteria E. coli and B. subtilis. The viability of acclimated strains was not affected under battery cycle conditions of 0.18-0.80 mA cm(-2) and 1.4-2.1 V. Bacterial addition within 1.0×10(10) cells mL(-1) did not significantly affect battery performance. Because the environmental stress inside the aqueous battery is specific, the use of this battery acclimation strategy may be of great potential for the breeding of industrial microorganisms.

Design and characterization of a new peptide vector for short interfering RNA delivery.

RNA interference holds tremendous potential as one of the most powerful therapeutic strategies. However, the properties of short interfering RNA (siRNA), such as hydrophilicity, negative charge, and instability in serum have limited its applications; therefore, significant efforts have been undertaken to improve its cellular uptake. Cell penetrating peptides have been utilized to deliver various biologically active molecules, such as proteins, liposomes, nanoparticles, peptide nucleic acids, and recently small interfering RNAs. Here, we introduce a new cell penetrating peptide GL1(Ac-GLWRAWLWKAFLASNWRRLLRLLR-NH2) to improve the intracellular uptake of siRNA. This peptide consists of four tryptophan residues that facilitated its binding with the cell membrane, five arginine residues and one lysine residue which are positively charged at physiological pH, which induced the formation of peptide-siRNA complexes and enhanced the affinity of the peptide and cell membrane. Moreover, GL1 adopted helical secondary structure due to the altered distribution of polar and nonpolar residues in the sequence. In this study, we investigated the effect of peptide/siRNA molar ratio on the particle size, surface charge, secondary structure, and uptake efficiency. The results showed that GL1 formed stable complexes with siRNA mainly through electrostatic interaction and hydrophobic interaction, and the complexes displayed a spherical shape with the size of ~100 nm and positive surface charge. Utilizing the techniques of fluorescence microscopy and flow cytometry, the intracellular localization of Cy3-labeled GAPDH siRNA was visualized and the cellular uptake was quantified. It is worth noting that in the serum free environment, compared to Lipofectamine 2000, GL1 achieved higher cellular uptake of siRNA (~95%); in the presence of serum, GL1 retained the same level of siRNA cellular uptake (~84%) as Lipofectamine 2000. In addition, the viability of cells treated by GL1 in all studied molar ratios was >85%, which was significantly higher than that treated by Lipofectamine 2000 (~70%). Taken together, the peptide GL1 demonstrated promise as a siRNA delivery system.

Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide.

A crucial bottleneck in RNA interference-based gene therapy is the lack of safe and efficient delivery systems. Here, a novel small interfering RNA (siRNA) delivery peptide, STR-HK, was constructed by conjugating a stearyl end to the N-terminus of the peptide sequence HHHPKPKRKV, where PKPKRKV is an altered sequence of the nucleus localization signal (PKKKRKV) and contributes to the cytosol localization of STR-HK-siRNA complexes. Histidine is a linker and plays an important role in disrupting the endosomal membrane via the proton sponge effect. As expected, STR-HK formed complexes with siRNA with a particle size of 80-160 nm in diameter and efficiently delivered Cy3-labeled glyceraldehyde 3-phosphate dehydrogenase siRNA into PC-3 human prostate cancer cells. The transfection efficiency of STR-HK at molar ratio of 60/1 was comparable to that of Lipofectamine 2000, one of the most efficient commercially available transfection reagents. Furthermore, the STR-HK-siRNA complexes exhibited minimal cytotoxicity, which was significantly lower than that of Lipofectamine. Taken together, the strategy of conjugating the stearyl moiety with HHHPKPKRKV as a non-viral siRNA delivery system is advantageous.

A novel peptide for efficient siRNA delivery in vitro and therapeutics in vivo.

Small interfering RNA (siRNA) shows great therapeutic potential due to its ability to regulate gene expression in a highly selective manner. However, its application has been limited by ineffective cellular uptake of siRNAs. To achieve successful gene-silencing efficiency, a safe and effective delivery vector is generally required. In this study, we designed a series of amphipathic peptides that comprised a variant of a nuclear localization sequence, 0-6 histidine residues and an optional stearic acid group. Among these candidates, STR-HK exhibited good characteristics as a safe and efficient siRNA delivery vector, facilitating efficient siRNA delivery to mammalian cells without causing cytotoxicity. Moreover, the intratumoral injection of STR-HK/siRNA complexes achieved high anti-tumor activity through the downregulation of the Bcl-2 protein in mice, with an inhibition rate of 62.8%. Our data demonstrate that STR-HK is a highly promising siRNA delivery vector for therapeutic applications.

Design and evaluation of endosomolytic biocompatible peptides as carriers for siRNA delivery.

Gene therapy using RNA interference (RNAi) technology has been explored to treat cancers, by regulating the expression of oncogene. However, even though small interfering RNA (siRNA), which triggers RNAi, may have great therapeutic potential, efforts at using them in vivo have been hampered by the difficulty of effective and safe delivery into cells of interest. In this study, to develop a safe and efficient carrier for in vitro and in vivo siRNA delivery, we designed a peptide library. These peptides are improved variants of a known peptide based siRNA carrier C6. All the modifications improved the transfection efficiency of C6 to some degree. After completing prescreening for activity, several promising candidates were used for further evaluation. Selected peptides C6M3 and C6M6 could form stable complexes with siRNA. These complexes could be greatly uptaken by cells and showed a punctate perinuclear distribution. Moreover, peptide/siRNA complexes achieved high transfection efficiency in vitro without inducing substantial cytotoxicity. We have validated the therapeutic potential of this strategy for cancer treatment by targeting Bcl-2 gene in mouse tumor models, and demonstrated that tumor growth was inhibited. In order to address possible immune side effects of these peptide carriers, biocompatibility study in terms of complement activation and cytokine activation assay were carried out, whereas none of the peptides induced such effects. In conclusion, these results support the potential of these peptides as therapeutic siRNA carrier.

In vitro and in vivo therapeutic siRNA delivery induced by a tryptophan-rich endosomolytic peptide.

At the forefront of medicine, gene therapy provides an effective way to treat a range of diseases by regulating defective genes at the root of the disease. Short interfering RNAs (siRNAs) hold great promise as therapeutic agents in this domain; however, intracellular delivery remains a major obstacle to clinical applications of therapeutic siRNAs. Here we report a peptide designed to mediate siRNA delivery. This peptide, C6M1, is rationally designed to promote the endosomal escape ability of an existing peptide sequence. Formed C6M1-siRNA nanoscale complexes are able to deliver siRNA into cells and induce specific gene knockdown with low toxicity. The increased membrane disruption ability under acidic conditions of the peptide with tryptophan residue substitution may contribute to the enhanced gene silence efficacy. Intratumoral injection of the complexes results in a marked reduction of tumor growth through downregulation of antiapoptotic Bcl-2 protein in mice. In addition, the C6M1-siRNA complex was proven safe at transfection concentration by cytotoxicity assay. These results demonstrate that the C6M1-siRNA complex is a potent system for efficient gene delivery in vitro and in vivo.

A new amphipathic, amino-acid-pairing (AAP) peptide as siRNA delivery carrier: physicochemical characterization and in vitro uptake.

RNA interference has emerged as a powerful tool in biological and pharmaceutical research; however, the enzymatic degradation and polyanionic nature of short interfering RNAs (siRNAs) lead to their poor cellular uptake and eventual biological effects. Among nonviral delivery systems, cell-penetrating peptides have been recently employed to improve the siRNA delivery efficiency. Here we introduce an 18-mer amphipathic, amino-acid-pairing peptide, C6, as an siRNA delivery carrier. Peptide C6 adopted a helical structure upon coassembling with siRNA. The C6-siRNA coassembly showed a size distribution between 50 and 250 nm, confirmed by dynamic light scattering and atomic force microscopy. The C6-siRNA interaction enthalpy and stoichiometry were 8.8 kJ·mol(-1) and 6.5, respectively, obtained by isothermal titration calorimetry. A minimum C6/siRNA molar ratio of 10:1 was required to form stable coassemblies/complexes, indicated by agarose gel shift assay and fluorescence spectroscopy. Peptide C6 showed lower toxicity and higher efficiency in cellular uptake of siRNA compared with Lipofectamine 2000. Fluorescence microscopy images also confirmed the localization of C6-siRNA complexes in the cytoplasm using Cy3-labeled siRNAs. These results indicate high capabilities of C6 in forming safe and stable complexes with siRNA and enhancing its cellular uptake.

[Effects of higeramine on hemodynamics and its tolerability and safety, an experimental study].

OBJECTIVE: To investigate the effects of higeramine (HG) on hemodynamics and its tolerability and safety so as to see if it can be used in cardiac loading test, and to compare the hemodynamic effects of HG and dobutamine (DB). METHODS: Six dogs were infused intrevenously with HG in escalating doses from l microgram/kg/min through 2 microgram/kg/min and to 4 microgram/kg/min, each dose being given for 5 minutes. Then the dogs were infused intravenously with DB at the escalating doses from 5 microgram/kg/min through 10 microgram/kg/min to 20 microgram/kg/min, each dose being given for 5 minutes. Heart rate (HR), blood pressure (BP), cardiac output (CO), myocardial oxygen consumption (MOC), and coronary blood flow (CBF) were measured at the beginning of test and by the end of each dose-infusion. Electrocardiography was conducted in the meantime. Left ventricular ejection fraction (LVEF) was measured with radionuclide equilibrium ventriculography. Another 8 dogs were given HG at the escalating doses from 1 microgram/kg/min up to 500 microgram/kg/min, each dose being infused for 3 minutes, to observe the tolerability and safety of HG, HR, BP, and ECG were monitored during the test. RESULTS: Intravenous administration of HG results in significant inotropic and chronotropic effects on the heart. HR, MOC, CO and CBF all increased in a dose-dependent manner in both HG and DB tests. HG did not cause significant change in systolic blood pressure (SBP), but a slight decrease in diastolic blood pressure (DBP) was found. HR increased steeply to the peak, and then remained at a plateau level. No significant ECG abnormality was seen except a few occasional premature ventricular beats. No dog died during the study. CONCLUSION: HG can be used in pharmacological stress test with remarkable tolerability and safety even at the dosage of 500 microgram/kg/min without serious adverse effect. It can be used as an alternative agent to DB under appropriate circumstances.

[Pharmacokinetics and relative bioavailability of probucol inclusion complex capsule in healthy dogs].

AIM: To study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule. METHODS: Following oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed. RESULTS: The concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240. CONCLUSION: The high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.