Dual SARS-CoV-2 and MERS-CoV inhibitors from Artemisia monosperma: isolation, structure elucidation, molecular modelling studies, and in vitro activities.

The COVID-19 pandemic has spread throughout the whole globe, so it is imperative that all available resources be used to treat this scourge. In reality, the development of new pharmaceuticals has mostly benefited from natural products. The widespread medicinal usage of species in the Asteraceae family is extensively researched. In this study, compounds isolated from methanolic extract of Artemisia monosperma Delile, a wild plant whose grows in Egypt's Sinai Peninsula. Three compounds, stigmasterol 3-O-ß-D-glucopyranoside 1, rhamnetin 3, and padmatin 6, were first isolated from this species. In addition, five previously reported compounds, arcapillin 2, jaceosidin 4, hispidulin 5, 7-O-methyleriodictyol 7, and eupatilin 8, were isolated. Applying molecular modelling simulations revealed two compounds, arcapillin 2 and rhamnetin 3 with the best docking interactions and energies within SARS-CoV-2 Mpro-binding site (-6.16, and -6.70 kcal mol-1, respectively). The top-docked compounds (2-3) were further evaluated for inhibitory concentrations (IC50), and half-maximal cytotoxicity (CC50) of both SARS-CoV-2 and MERS-CoV. Interestingly, arcapillin showed high antiviral activity towards SARS-CoV-2 and MERS-CoV, with IC50 values of 190.8 µg mL-1 and 16.58 µg mL-1, respectively. These findings may hold promise for further preclinical and clinical research, particularly on arcapillin itself or in collaboration with other drugs for COVID-19 treatment.

Altered Levels of Natural Autoantibodies against Heat Shock Proteins in Pregnant Women with Hashimoto's Thyroiditis.

The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study's objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.

Laparoscopic anatomic vs. nonanatomic liver resection for large hepatocellular carcinoma (≥5 cm) in the right lobe.

OBJECTIVE: To determine the impacts and outcomes of laparoscopic anatomic liver resection (LAR) and laparoscopic nonanatomic resection (LNAR) in patients with large hepatocellular carcinoma (HCC) in the right lobe of the liver. BACKGROUND: There are few comparative studies of LAR and LNAR for large HCC. METHOD: Three hundred thirty-seven patients underwent liver resection for large HCC (≥5 cm) at Seoul National University Bundang Hospital, Seoul, Korea, between January 2004 and December 2022. After the exclusion of patients treated with open hepatic resection and those who had left-lobe or bilobar tumors, 94 patients were ultimately included. Patients were divided into LAR group (61 patients) and LNAR group (33 patients). After propensity score matching (PSM) with 1:1 matching, 31 patients were included in each group. The outcomes in the two groups were compared. RESULTS: LAR group had longer operative time than LNAR group (333.7 ± 113.7 vs 210 ± 117.6 min, respectively, P < 0.001), wider safety margin (1.4 ± 1.5 vs 0.7 ± 0.7 cm, respectively, P = 0.015), and lower incidence of recurrence (25.8% vs. 54.8%, respectively, P = 0.021). CONCLUSION: LAR required longer operative time, achieved wider safety margin, and had lower incidence of recurrence than LNAR.

Valorization of lignocellulosic wastes for sustainable xylanase production from locally isolated Bacillus subtilis exploited for xylooligosaccharides' production with potential antimicrobial activity.

The worldwide availability of lignocellulosic wastes represents a serious environmental challenge with potential opportunities. Xylanases are crucial in lignocellulosic bio-hydrolysis, but the low enzyme productivity and stability are still challenges. In the current study, Bacillus subtilis (coded ARSE2) revealed potent xylanase activity among other local isolates. The enzyme production optimization revealed that maximum enzyme production (490.58 U/mL) was achieved with 1% xylan, 1.4% peptone, and 5% NaCl at 30 °C and pH 9. Furthermore, several lignocellulosic wastes were exploited for sustainable xylanase production, where sugarcane bagasse (16%) under solid-state fermentation and woody sawdust (2%) under submerged fermentation supported the maximum enzyme titer of about 472.03 and 485.7 U/mL, respectively. The partially purified enzyme revealed two protein bands at 42 and 30 kDa. The partially purified enzyme revealed remarkable enzyme activity and stability at 50-60 °C and pH 8-9. The enzyme also revealed significant stability toward tween-80, urea, DTT, and EDTA with Vmax and Km values of 1481.5 U/mL and 0.187 mM, respectively. Additionally, the purified xylanase was applied for xylooligosaccharides production, which revealed significant antimicrobial activity toward Staphylococcus aureus with lower activity against Escherichia coli. Hence, the locally isolated Bacillus subtilis ARSE2 could fulfill the xylanase production requirements in terms of economic production at a high titer with promising enzyme characteristics. Additionally, the resultant xylooligosaccharides revealed a promising antimicrobial potential, which paves the way for other medical applications.

Comparison between two mathematical methods to estimate arterial occlusion pressure and tourniquet effectiveness in lower limb surgery: a prospective, randomized, double blind, comparative study.

The effectiveness of two different methods for calculating the arterial occlusion pressure (AOP) to set tourniquet inflation pressures were assessed in patients underwent knee arthroscopy. Eighty patients were included in this study. Tourniquet inflation pressure was set by adding 20 mmHg of safety margin above the AOP value which was calculated by either the Tuncali et al. formula or Hong-yun Liu et al. formula. Primary outcome measures were the initial and maximum SBP, initial and maximum tourniquet inflation pressure, the secondary outcomes were the surgeon rating of the bloodlessness of the surgical field and tourniquet associated complications. There was significant difference in the initial tourniquet pressure (mmHg); it was 208 ± 12 and 262 ± 18 for group (A) and (B) respectively; also there was significant difference in the maximum tourniquet pressure (mmHg), it was 229 ± 14 and 283 ± 19 for group (A) and (B) respectively. There was no significant difference in the initial SBP-to- tourniquet inflation time, the initial SBP or the maximum SBP between the groups. Also, there was no significant difference in surgeon rating of the bloodlessness of the surgical field, at the start, middle and end of surgery. Hong-yun Liu et al. mathematical formula was found to be less effective than Tuncali et al. formula to estimate the least effective tourniquet pressure in lower limb surgery and we might consider it invalid to be used in the lower limb.Clinical trials registration number: NCT03706859 (Clinicaltrials.gov) and registration date: January, 2019. https://clinicaltrials.gov/ct2/show/NCT03706859.

Histological and Anthropometric Changes in the Aging Nose.

BACKGROUND: Rhinoplasty in the elderly requires different surgical approaches due to the morphological and structural changes affecting the nose over time. OBJECTIVES: In this study, the authors aimed to evaluate the age-related cellular and architectural changes of nasal cartilages and soft tissue attachments. METHODS: This prospective study included 80 patients who underwent rhinoplasty. Patients were divided into 2 groups according to age. Group I included 40 patients ranging in age from 19 to 39 years. Group II included 40 patients aged at least 40 years. Samples from nasal cartilages (upper lateral, lower lateral, and septum) and nasal attachments (interdomal, inter-cartilaginous, and septo-crural) were taken. All specimens were evaluated histologically to detect age-related changes. A modified version of the Mankin grading scale was used to score each nasal cartilage sample. All attachment samples were examined by image analysis for quantitative assessment. The results were correlated to preoperative anthropometric measurements of nasolabial angle and nasal projection. RESULTS: Histologically, in group II, the cartilage matrix showed fibrinoid degeneration with a significant decrease in the number of chondrocytes and increased perichondrial fibrosis compared with group I. Attachments in group II showed a lower number of blood vessels and decreased percentage of collagen bundles. Modified Mankin scores were significantly higher in group II, indicating weak cartilages compared with group I. There was negative correlation and significance between projection, nasolabial angle, cartilages, and attachments in study groups. The linear regression model revealed that the lower lateral cartilage is the cartilage that is most affected by the aging process. CONCLUSIONS: These findings not only enhance our current understanding of the natural changes that occur in the nose during aging but may also affect surgical decision-making when grafting or suturing are considered during rhinoplasty.Level of Evidence: 2.

The role of Gabapentin oral solution in decreasing desflurane associated emergence agitation and delirium in children after stabismus surgery, a prospective randomized double-blind study.

BACKGROUND: Short acting inhalational anesthetic (Desflurane) produces emergence agitation (EA) in pediatrics with an incidence up to 80%. The aim of the present study was to examine the role of Gabapentin oral solution in attenuating desflurane associated EA in children after strabismus surgery under general anesthesia. METHODS: Seventy patients, 2-6 years old, scheduled for strabismus surgery were randomly allocated into two groups (35 each); Control group (c): received 5 ml of oral strawberry juice (placebo) and Gabapentin group (G) received 5 mg/Kg gabapentin oral solution in 5 ml strawberry juice, 1 h before anesthesia. Patient separation, cooperation, emergence incidence and emergence severity were assessed. Also time to extubation and time to emergence, duration of PACU stay, PONV and number of patients required meperidine postoperatively were recorded. RESULTS: Duration to extubation and duration to emergence were statistically prolonged in gabapentin group compared to the control group. The incidence of EA and its severity were reduced in gabapentin group with more tendencies to be asleep and less attentive. More patients in the control group required postoperative meperidine to reduce crying and agitation. CONCLUSION: Oral gabapentin 5 mg/kg reduced the incidence and severity scoring of emergence agitation (by 20%) with more tendencies for sleeping with preserved response to stimuli in PACU. TRIAL REGISTRATION: Number: NCT03347916 , date: November 17, 2017, retrospectively.

Accelerated Coasting Does Not Affect Oocyte Maturation.

AIMS: The study aimed to assess the efficacy of accelerating the process of coasting through adding gonadotropin releasing hormone (GnRH) antagonist (GnRH-ant) on the day of triggering of oocyte maturation without withholding the GnRH agonist (GnRHa) in women at risk for developing ovarian hyperstimulation syndrome (OHSS). METHODS: Retrospective case-control study of the outcomes of GnRHa cycles in which women were at risk to develop OHSS. Women who underwent acceleration of coasting (n = 50) were compared with a control group of women who underwent usual coasting (n = 57). RESULTS: The oocyte maturation and fertilization rates were significantly higher in the accelerated coasting group than in the usual coasting group (83.05 vs. 67.62%; p < 0.001 and 79.85 vs. 65.84%; p < 0.001, respectively). The pregnancy rates were higher in the accelerated coasting group than in the usual coasting group but without statistically significant difference. The incidences of mild, moderate, and severe OHSS were not significantly different between both groups. CONCLUSION: Acceleration of coasting in cases of OHSS through treatment with GnRH-ant after pituitary suppression with GnRHa offered a novel approach to reduce estradiol level, avoid cycle cancellation, and maintain excellent oocyte maturation rate and thus high pregnancy rate with prevention of OHSS.

Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies.

OBJECTIVES.: The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis. METHODS.: The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-γ and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used. RESULTS.: Combined treatment of MSC with IL-22, IFN-γ and TNF resulted in increased MSC proliferation ( P = 0.008) and migration ( P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated by IL-22 alone ( P < 0.05). MSC osteogenesis was enhanced following IL-22 exposure ( P = 0.03, measured by calcium production). The combination of IFN-γ and TNF with or without IL-22 suppressed MSC osteogenesis ( P = 0.03). CONCLUSION.: This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments, with MSC osteogenesis occurring only in the absence of IFN-γ/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.

Vaginal progesterone for prevention of preterm labor in asymptomatic twin pregnancies with sonographic short cervix: a randomized clinical trial of efficacy and safety.

PURPOSE: To evaluate the value of vaginal progesterone therapy for reduction of preterm labor in asymptomatic women with twin pregnancies and sonographic short cervix. METHODS: This randomized controlled study was conducted in Mansoura University Hospital and private practice settings in Mansoura, Egypt. Of 322 women with dichorionic twin pregnancy, 250 asymptomatic women with cervical length of 20-25 mm at 20-24 weeks of gestation were included in the study. All women were randomly divided into two groups; the study group (n = 125) received vaginal progesterone suppositories in a dose of 400 mg daily starting at 20-24 weeks of gestation while the control group (n = 125) received no treatment. The primary outcome measure was preterm labor before 34 weeks of gestation and the secondary outcome measures were neonatal respiratory distress syndrome (RDS) and early neonatal death (END). RESULTS: 224 women (116 in the study group and 108 in the control group) were subjected to final analysis. The duration of pregnancy was significantly longer in the study group and the incidence of preterm labor before 34 and 32 weeks of gestation was significantly lower in the study group. The neonatal morbidities and mortality were significantly lower in the study group as shown by lower incidence of very low (<1500 gm) birth weight, neonatal RDS, the need for mechanical ventilation and END. CONCLUSIONS: Vaginal progesterone administration in asymptomatic twin pregnancies with sonographic short cervix (20-25 mm) at 20-24 weeks of gestation is effective and safe treatment for reducing the incidence of preterm labor with subsequent reduction in the neonatal morbidities and mortality associated with preterm birth.

Population structure of natural and propagated isolates of Cryptosporidium parvum, C. hominis and C. meleagridis.

The three protozoan species Cryptosporidium parvum, C. meleagridis and C. hominis (phylum Apicomplexa) are enteric pathogens of humans. The former two species are zoonotic and the latter is thought to infect only humans. To better characterize the structure and transmission of natural and laboratory-propagated isolates, we analyzed a collection of archived human and animal isolates of these three species by deep-sequencing polymerase chain reaction products amplified from a polymorphic sequence on chromosome 1. Thousands of screened 200-nucleotide sequences were analyzed to compare the diversity among samples, to assess the impact of laboratory propagation on population complexity and to identify taxonomically mixed isolates. Contrary to our expectation, repeated propagation in animals did not reduce intra-isolate diversity nor was diversity associated with host species. Significantly, in most samples, sequences characteristic of a different species were identified. The presence of C. hominis alleles in C. parvum and C. meleagridis isolates confirms earlier reports of mixed isolates and raises the possibility that the host range of C. hominis is broader than typically assumed. In a genetically divergent isolate of C. parvum, a majority of sequences was found to be recombinant, suggesting that this genotype originated from a C. parvum × C. hominis recombination event.

Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.

This prospective randomized controlled trial evaluated the effect of combined oral coenzyme Q10 (CoQ10) and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). A total of 101 infertile women with PCOS resistant to clomiphene citrate were randomized either to combined CoQ10 and clomiphene citrate (51 patients, 82 cycles) or to clomiphene citrate alone (50 patients, 71 cycles). The outcome measures were number of follicles, serum oestradiol, serum progesterone, endometrial thickness and ovulation, clinical pregnancy and miscarriage rates. Numbers of follicles >14 mm and ≥18 mm were significantly higher in the CoQ10 group. Endometrial thickness on the day of human chorionic gonadotrophin was significantly greater in the CoQ10 group (8.82 ± 0.27 mm versus 7.03 ± 0.74 mm). Ovulation occurred in 54/82 cycles (65.9%) in the CoQ10 group and 11/71 cycles (15.5%) in the control group. Clinical pregnancy rate was significantly higher in the CoQ10 group (19/51, 37.3%) versus the control group (3/50, 6.0%). Combination of CoQ10 and clomiphene citrate in the treatment of clomiphene-citrate-resistant PCOS patients improves ovulation and clinical pregnancy rates. It is an effective and safe option and can be considered before gonadotrophin therapy or laparoscopic ovarian drilling.

Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection.

PURPOSE: Polycystic ovary syndrome (PCOS) is associated with oxidative stress (OS) and serum superoxide dismutase (SOD) activity has been reported with mixed results. The objective of this study was to examine the activity of SOD both in the serum and FF from women with PCOS undergoing ICSI, as well as the expression of Cu/Zn-SOD mRNA in the cells recovered from the FF. METHODS: Forty women undergoing an ICSI trial were divided into: group I, included 20 PCOS cases, group II included 20 age-matched controls with tubal factor infertility. Both groups were similarly stimulated. A total of 204 metaphase II (MII) oocytes were aspirated; (108) from PCOS, and (96) from the control group. SOD activities in the serum and FF, as well as Cu/Zn-SOD (SOD1) mRNAs in follicular fluid (FF) cells were analyzed. RESULTS: There was a statistically highly significant decrease (p < 0.001) both in the mean serum SOD (45.56 ± 18.06) and FF SOD activity (42.49 ± 11.46) in PCOS than the control group (77.38 ± 7.82), (74.37 ± 6.15) respectively. The mean relative levels of Cu, Zn SOD mRNAs was significantly lower (p < 0.001) in cells isolated from the FF in PCOS (0.36 ± 0.14) than the control group (0.81 ± 0.15). SOD activity in FF had no effects on fertilization rate (p > 0.05), or embryo quality after intracytoplasmic sperm injection (ICSI). CONCLUSION: Although decreased SOD activity in FF has no effect on fertilization rate and/or embryo quality, serum SOD activity could be a clinical parameter for determining systemic oxidative stress in PCOS.

PERMMA: Enhancing parameter estimation of software reliability growth models: A comparative analysis of metaheuristic optimization algorithms.

Software reliability growth models (SRGMs) are universally admitted and employed for reliability assessment. The process of software reliability analysis is separated into two components. The first component is model construction, and the second is parameter estimation. This study concentrates on the second segment parameter estimation. The past few decades of literature observance say that the parameter estimation was typically done by either maximum likelihood estimation (MLE) or least squares estimation (LSE). Increasing attention has been noted in stochastic optimization methods in the previous couple of decades. There are various limitations in the traditional optimization criteria; to overcome these obstacles metaheuristic optimization algorithms are used. Therefore, it requires a method of search space and local optima avoidance. To analyze the applicability of various developed meta-heuristic algorithms in SRGMs parameter estimation. The proposed approach compares the meta-heuristic methods for parameter estimation by various criteria. For parameter estimation, this study uses four meta-heuristics algorithms: Grey-Wolf Optimizer (GWO), Regenerative Genetic Algorithm (RGA), Sine-Cosine Algorithm (SCA), and Gravitational Search Algorithm (GSA). Four popular SRGMs did the comparative analysis of the parameter estimation power of these four algorithms on three actual-failure datasets. The estimated value of parameters through meta-heuristic algorithms are approximately near the LSE method values. The results show that RGA and GWO are better on a variety of real-world failure data, and they have excellent parameter estimation potential. Based on the convergence and R2 distribution criteria, this study suggests that RGA and GWO are more appropriate for the parameter estimation of SRGMs. RGA could locate the optimal solution more correctly and faster than GWO and other optimization techniques.