Tri-substituted 1,3,5-triazine-based analogs as effective HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs): A systematic review.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as different combinations of NNRTIs have been used on clinically approved combining highly active antiretroviral therapy (HAART) to resist the growth of HIV-1 and decrease the mortality rate of HIV/AIDS. Although the feeble strength against the drug-resistant mutant strains and the long-term damaging effects have been reducing the effectiveness of HAART, it could be a crucial challenge to develop novel Anti-HIV leads with a vital mode of action and the least side effects. The extensive chemical reactivity and the diverse chemotherapeutic applications of the 1,3,5-triazine have provided a wide scope of research in medicinal chemistry via a structural modification. In this review, we focused on the Anti-HIV profile of the tri-substituted s-triazine derivatives with structure-based features and also discussed the active mode of action to evaluate the significant findings. The tri-substituted 1,3,5-triazine derivatives have been found more promising to inhibit the growth of the drug-sensitive and drug-resistant variants of HIV-1, especially HIV-1 wild-type, HIV-1 K103N/Y181C, and HIV-1 Tyr181Cys. It has been observed that these derivatives have interacted with the enzyme protein residues via a significant π $\pi $ - π $\pi $ interaction and hydrogen bonding to resist the proliferation of the viral genomes. Further, the SAR and the active binding modes are critically described and highlight the role of structural variations with functional groups along with the binding affinity of targeted enzymes, which may be beneficial for rational drug discovery to develop highly dynamic Anti-HIV agents.

Arylidene and amino spacer-linked rhodanine-quinoline hybrids as upgraded antimicrobial agents.

Antibiotic resistance associated with various microorganisms such as Gram-positive, Gram-negative, fungal strains, and multidrug-resistant tuberculosis increases the risk of healthcare survival. Preliminary therapeutics becoming ineffective that might lead to noteworthy mortality presents a crucial challenge for the scientific community. Hence, there is an urgent need to develop hybrid compounds as antimicrobial agents by combining two or more bioactive heterocyclic moieties into a single molecular framework with fewer side effects and a unique mode of action. This review highlights the recent advances (2013-2023) in the pharmacology of rhodanine-linked quinoline hybrids as more effective antimicrobial agents. In the drug development process, linker hybrids acquire the top position due to their excellent π-stacking and Van der Waals interaction with the DNA active sites of pathogens. A molecular hybridization strategy has been optimized, indicating that combining these two bioactive moieties with an arylidene and an amino spacer linker increases the antimicrobial potential and reduces drug resistance. Moreover, the structure-activity relationship study is discussed to express the role of various functional groups in improving and decrementing antimicrobial activities for rational drug design. Also, a linker approach may accelerate the development of dynamic antimicrobial agents through molecular hybridization.

Noncontact diffuse optical assessment of blood flow changes in head and neck free tissue transfer flaps.

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning "1") for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89 ± 0.15, 2.26 ± 0.13, and 2.43 ± 0.13 (mean ± standard error), respectively, on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (p<0.001), indicating a gradual recovery of flap vascularity after the tissue transfer. By contrast, rBF changes observed from the unsuccessful flaps were 1.14 and 1.34, respectively, on postoperative days 2 and 4, indicating less flow recovery. Measurement of BF recovery after flap anastomosis holds the potential to act early to salvage ischemic flaps.

Facile synthesis of benzonitrile/nicotinonitrile based s-triazines as new potential antimycobacterial agents.

A common strategy to synthesize 4/6-(4-(4-methylpiperazin-1-yl)-6-(4-(4-oxo-2-phenylthiazolidin-3-yl)phenyl)-1,3,5-triazin-2-yloxy)benzonitriles/nicotinonitriles was developed by applying an efficient palladium-catalyzed C-C Suzuki coupling. Moreover, the synthesized compounds were also tested for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using BACTEC MGIT and Lowenstein-Jensen MIC methods. Several compounds displayed profound antimycobacterial activity in combination with low toxicity towards mammalian cells. The best results were observed amongst the nicotinonitrile substituted s-triazine analogs and it could be a potential starting point to develop new lead compounds in the fight against M. tuberculosis H37Rv. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analysis.

A double-blind, randomized, placebo-controlled health-outcomes survey of the effect of botulinum toxin type a injections on quality of life and self-esteem.

BACKGROUND: Although studies show that botulinum toxin type A (BoNTA) can positively influence one's first impression, little research has been conducted to measure the effect that BoNTA has on mental well-being. OBJECTIVE: To determine the effects that BoNTA injections for the treatment of facial wrinkles had on quality of life (QOL) and self-esteem. METHODS AND MATERIALS: One hundred participants received treatment with BoNTA or placebo saline in this double-blind randomized placebo-controlled survey. All participants completed a health outcomes survey consisting of Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form and Heatherton and Polivy State Self-Esteem measurements before injection and 2 weeks and 3 months after injection. RESULTS: Statistically significant improvements (p<.05) in participants treated with BoNTA were observed in answers to QOL questions regarding physical health, mood, household activities, overall life satisfaction, body satisfaction, self-consciousness, intellect, self-worth, appearance, comprehension, weight satisfaction, attractiveness, and sense of well-being. Increases in overall self-esteem and appearance-, social-, and performance-related self-esteem were observed in participants treated with BoNTA. CONCLUSION: Our findings showed that BoNTA injections result in improvements in QOL and self-esteem. In addition, BoNTA-naïve participants demonstrate greater improvements in QOL and self-esteem than participants previously exposed to BoNTA. Moreover, BoNTA-familiar participants demonstrated sustained improvement in QOL and self-esteem relative to BoNTA-naïve participants, even when injected with placebo.

Extended superficial muscular aponeurotic system rhytidectomy: a graded approach.

Surgical approaches for rhytidectomy continue to evolve. For the past 26 years, the senior author has used a graded approach in combination with the modified deep-plane facelift, consistently achieving natural-appearing results and satisfied patients. This article outlines the analysis of the patient, preoperative preparation of the patient, an algorithm for adjunctive procedures to achieve a youthful yet balanced face, the associated surgical technique, and also possible complications.

Brow-lift: subgaleal vs subperiosteal flap adherence in the rabbit model.

OBJECTIVE: To analyze and compare the postoperative adherence qualities between the subperiosteal layer approach and the subgaleal layer approach for brow elevation using a rabbit model. METHODS: Twelve New Zealand white rabbits (weight, 3.1-3.5 kg) were evenly divided into 2 groups and underwent forehead flap elevation via subperiosteal or subgaleal dissection, depending on the group assignment. Two rabbits were not operated on and served as controls. Histologic and biomechanical testing (tensiometer) was performed at 2, 4, 6, 8, and 10 weeks to assess adherence and wound strength. RESULTS: The subgaleal flap strength was greater than that of the subperiosteal flap at each time point. The mean flap strength for the subgaleal and subperiosteal control subjects were 208 g and 706 g, respectively. These values approximately correspond with the postelevation subgaleal flap strength regained at 2 weeks and the postelevation subperiosteal flap strength regained at 8 weeks. On histologic analysis, the subgaleal specimen showed less intervening space and a greater degree of connective tissue proliferation than the subperiosteal specimen at as early as 4 weeks. CONCLUSION: This study supports our hypothesis that rapid healing and early fixation occurs when the subgaleal approach is used for surgical brow elevation.

Correcting the short nose in revision rhinoplasty.

The scope of this article is directed toward strategic planning and surgical treatment of the postoperative short nose deformity. Emphasis is placed on controlled repositioning of the central compartment of the nose (tip and columella), followed by moving the nostrils back into a more natural position with the use of autologous grafting techniques. The overall goal is to achieve the desired esthetic transformation while maximizing nasal function with good long-term results.

Heat-shock protein 25 ameliorates calcium oxalate crystal-mediated oxidative stress in renal epithelial cells.

OBJECTIVE: To investigate whether the antioxidant protection attributed to small heat-shock proteins (sHSPs) affects calcium oxalate stone formation, a pro-oxidant disease. MATERIALS AND METHODS: Canine distal tubular epithelial cells (Madin-Darby canine kidney, MDCK cells) were grown as confluent monolayers. Treatment regimens included control and HS-treated cells (37 degrees C and 42 degrees C for 1 h) with or without calcium oxalate monohydrate (COM) or free oxalate treatment (28 microg/cm2) 16 h later. In digitonin-permeabilized cells, O2- was measured by lucigenin-enhanced chemiluminescence over a 5-min period, to measure mitochondrial O2- production. Protein expression was assessed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis Western blot analysis using specific antibodies. RESULTS: COM significantly increased O2- production in MDCK cells. HS treatment, which up-regulated HSP25 expression, significantly decreased this O2- production (P < 0.05) but had no effect in control cells. In COM-treated cells (20 h) there was a marked and significant down-regulation of both HSP 25, HSP 70 and heme oxygenase-1 expression compared to cells treated with HS alone (P < 0.05). Free oxalate had no effect on HSP 25 expression. CONCLUSIONS: The results suggest that the COM-induced increase in mitochondrial O2- production in MDCK cells is ameliorated by HSP 25 up-regulation via HS. Specific COM inhibition of HSP 25, HSP 70 and heme oxygenase-1 up-regulation suggests that COM-induced reactive oxygen species damage is unable to benefit from HSP-associated physiological resistance.