Synergism of d-limonene and temozolomide on migratory and apoptotic behaviors of human glioblastoma cell lines.

Introduction: Glioblastoma (GBM), which is a heterogeneous and aggressive type of brain tumor, is known for its poor survival outcomes. The treatment of GBM remains challenging primarily due to the drug resistance to the current standard therapeutic option, temozolomide (TMZ). Researchers are currently focusing on developing an appropriate alternative combinatorial therapeutic to enhance treatment outcomes. D-limonene (DL) is a monoterpene derived from citrus fruit. This study aims to assess the impact of combining DL with TMZ and explore its potential mechanism of action in U87MG and LN229 GBM cells. Methods: The effects of the combined treatment of DL and TMZ were assessed on various cellular aspects, including cell viability, anchorage-independent cell growth, and DNA damage. Furthermore, the influence of this combination on cell cycle progression, cell migration, and cell death was also investigated. Results: The combination of DL+TMZ demonstrated a synergistic effect, resulting in reduced cell proliferation and suppressing the colony formation ability of a single cell. Treatment with DL and TMZ arrested the cells in G0/G1 phase. Furthermore, the DL+TMZ combination induced apoptosis by upregulating the expression of Bax, and Caspase (CASP)-3, while reducing the expression of the Bcl-2 gene in GBM cells. In addition, the combined treatment of DL+TMZ significantly decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9, expression, indicating inhibition of cell migration in GBM cells. Conclusion: In conclusion, the combination of DL and TMZ demonstrated a synergistic effect in reducing cell proliferation, suppressing colony formation, inducing apoptosis, and inhibiting cell migration in GBM cells. These findings suggest the potential of DL+TMZ combination therapy as an effective treatment for GBM.

Comparative analysis of α-pinene alone and combined with temozolomide in human glioblastoma cells.

α-Pinene (PEN) is a phyto compound present in terpene plants. In traditional medicine, PEN has been used for its anti-inflammatory, pain-relieving, and bronchodilator properties. The effect of PEN in combination with temozolomide (TMZ) in glioblastoma multiforme (GBM) cells has been evaluated. The action of the PEN + TMZ combination on cell migration, soft-agar, and cell death was determined in LN229 and U87MG human glioblastoma cells. In combination, PEN with TMZ showed a synergistic inhibitory effect in the GBM cells. The PEN + TMZ treatment showed a higher fluorescent intensity and reduced the percentage of wound area closure compared to the compound alone. The compounds in combination also resulted in a reduction in single-cell colony formation. To conclude, the study showed that plant-derived PEN enhanced the effectiveness of standard chemotherapeutic, TMZ, in LN229 and U87MG cells.

Intracameral Drug Delivery: A Review of Agents, Indications, and Outcomes.

An intracameral (IC) injection directly delivers the drug into the anterior chamber of the eye. This targeted drug delivery technique overcomes the ocular barriers and offers a high therapeutic concentration of medication at the desired site and consequently better clinical outcomes. IC drug delivery is a safe and effective modality with many advantages over topical delivery. These include excellent bioavailability, reduced systemic risk, and minimal ocular toxicity. Agents delivered via IC injection have shown promising results against infection, inflammation, ocular hypertension, and neovascularization. Current literature shows that IC antibiotics, including cefuroxime, vancomycin, and moxifloxacin, are routinely used for prophylaxis of endophthalmitis. Other drugs available for IC use are steroids, anesthetics, mydriatics, miotics, antivascular endothelial growth factor, antiglaucoma, and alkylating agents. Introduction of sustained-release devices containing dexamethasone or Bimatoprost in anterior chamber via IC route has the potential in treating ocular inflammation and raised intraocular pressure. The complications such as hemorrhagic occlusive retinal vasculitis and toxic anterior segment syndrome have been documented with IC prophylaxis but are rare. In this review, we provide an overview of available IC drugs, their pharmacokinetics, the spectrum of activity, dosage and preparation, prophylactic and therapeutic usage, clinical efficacy, and safety profiles.

Rhino-orbito-cerebral mucormycosis and its resurgence during COVID-19 pandemic: A review.

This study aimed to review the current literature for epidemiology, pathogenesis, clinical spectrum and management of rhino-orbito-cerebral-mucormycosis (ROCM), especially highlighting the association between ROCM and COVID-19 disease and factors resulting in its resurgence during the pandemic. Mucormycosis is a rare, but an important emerging opportunistic fungal infection, often associated with high morbidity and mortality. ROCM is the commonest and also the most aggressive clinical form occurring in debilitated patients in conjunction with sinus or para-sinus involvement due to the propensity for contiguous spread. Recently ROCM has shown an unprecedented resurgence during the current pandemic. Reports from different parts of the world indicated an increased risk and incidence of ROCM in patients who had required hospital admission and have recovered from moderate-to-severe COVID-19 disease. A majority of mucormycosis cases have been reported from India. The presence of diabetes mellitus (DM) and use of corticosteroids for COVID-19 pneumonia were found to be the key risk factors, resulting in higher mortality. Amidst the ongoing pandemic, with the third wave already having affected most of the world, it becomes imperative to adopt a risk-based approach toward COVID-19 patients predisposed to developing ROCM. This could be based on the most recently published literature and emerging data from centers across the world. The present review intended to elucidate the causes that brought about the current spike in ROCM and the importance of its early detection and management to reduce mortality, loss of eye, and the need for mutilating debridement.

Combinatorial Effect of Temozolomide and Naringenin in Human Glioblastoma Multiforme Cell Lines.

Glioblastoma multiforme (GBM) is a grade IV, lethal, and the most common type of brain tumor. GBM can acquire resistance to temozolomide (TMZ) recommended for its treatment. Naringenin (NAG), a flavonoid generally found in grapefruit, has antioxidant, anti-proliferative, and anti-inflammatory properties. It has been reported that phytochemicals can reduce resistance and improve the efficacy of a chemo-resistant drug. The combinatorial effect of TMZ and NAG on cell proliferation was evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay, and the apoptosis in the U87MG and LN229 GBM cells were evaluated by change in fluorescence intensity. The effect of NAG and TMZ on anchorage-independent single-cell colony formation and cell migration was investigated. NAG and TMZ demonstrated enhanced cytotoxic effects on U87MG and LN229 cell lines. The combination index value being less than one indicated the synergistic action of the two drugs in restricting the growth of the cells. The NAG and TMZ together resulted in higher fluorescence intensity as compared to the alone drug. Further, the study showed a marked reduction in the migration of the cells and the formation of a single cell colony.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952438.

Comparison of Clinical Outcomes and Visual Quality Using a Medium Versus Small Contact Glass in Patients Undergoing SMILE With Large Corneal Diameters.

PURPOSE: To compare the clinical outcomes and visual quality using a small (S) versus medium (M) size contact glass in eyes with large white-to-white (WTW) distance undergoing bilateral small incision lenticule extraction (SMILE) for myopia correction. METHODS: This contralateral eye study involved 60 eyes of 30 patients (mean age: 27.20 years) undergoing bilateral SMILE for myopia/myopic astigmatism with a WTW distance of 12 mm or greater in both eyes, which were randomized to receive treatment with an S-contact glass in one eye and an M-contact glass in the fellow eye. Opaque bubble layer (OBL) was graded using a new grading system. On postoperative 1 day, 2 weeks, and 3 months, UDVA, CDVA, contrast sensitivity, Objective Scatter Index, and modulation transfer function cut-off values were compared between the two groups. RESULTS: The mean OBL score was significantly lower in the S-contact glass group (28.18%) compared to the M-contact glass group (67.13%) (P < .01). At 1 day postoperatively, the UDVA, Objective Scatter Index score, and contrast sensitivity values for all spatial frequencies were significantly better in eyes treated with the S-contact glass compared to the M-contact glass (P ⩽ .05). At 3 months postoperatively, however, the UDVA, Objective Scatter Index score, modulation transfer function cut-off, and contrast sensitivity values were comparable for both groups. No eye in either group had intraoperative complications such as suction loss, incision/lenticule tears, or lenticule retention. CONCLUSIONS: In corneas with a WTW distance of 12 mm or greater, docking with the S-contact glass resulted in significantly better immediate visual results due to less OBL formation and smoother tissue dissection compared to the M-contact glass. [J Refract Surg. 2021;37(3):150-157.].

Feasibility, Safety, and Outcomes With Standard Versus Differential Spot Distance Protocols in Eyes Undergoing SMILE for Myopia and Myopic Astigmatism.

PURPOSE: To study the feasibility, safety, comparison of intraoperative ease of dissection, and immediate visual outcomes with standard versus differential small incision lenticule extraction (SMILE) spot settings in eyes undergoing bilateral SMILE for myopia or myopic astigmatism. METHODS: One hundred eyes of 50 patients (mean age: 25.4 years) were randomized to receive standard settings (4.5-µm spot and track spacing in cap and lenticule interface) in one eye and differential settings (4.5-µm spot and track spacing in cap interface and 4.2 µm in lenticule interface) in the contralateral eye. Opaque bubble layer (OBL) was graded using a new grading system and a surgeon questionnaire was obtained to grade the ease of dissection (from 0 to 5, with 5 being the easiest) at the end of each surgery. Visual results and optical quality were analyzed at 1 day, 2 weeks, and 3 months postoperatively. RESULTS: The mean OBL score was significantly lower in the differential group (26.3%) compared to the standard group (35.3%) (P < .01). Consequently, the mean dissection score was significantly higher in the differential group (4.01) compared to the standard group (3.57) (P < .01). The uncorrected distance visual acuity, Objective Scatter Index, modulation transfer function cut-off, and higher order aberrations were comparable with no statistically significant difference between both groups at 1 day, 2 weeks, and 3 months postoperatively (P > .05 for all parameters). No eye in either group had any intraoperative or postoperative complication affecting visual recovery. CONCLUSIONS: Differential spot settings resulted in less intraoperative OBL and easy separability. However, the visual results and optical quality were comparable between groups. [J Refract Surg. 2021;37(5):294-302.].

Visual and Refractive Outcomes With the Eyecryl Phakic Toric IOL Versus the Visian Toric Implantable Collamer Lens: Results of a 2-Year Prospective Comparative Study.

PURPOSE: To compare the 2-year visual and refractive outcomes with the Eyecryl Phakic Toric IOL (EP TIOL) (Biotech Vision Care Pvt Ltd) and Visian Toric ICL (TICL) (STAAR Surgical) for correction of high myopic astigmatism. METHODS: This prospective, interventional, non-randomized comparison study included eligible patients who underwent toric phakic IOL surgery in one or both eyes with either the EP TIOL or TICL for myopic astigmatism. Two years postoperatively, both lenses were compared for their safety, efficacy, stability, and patient satisfaction. Vector analysis of astigmatism was performed using the Alpins method with the ASSORT software (ASSORT Party Ltd). RESULTS: A total of 50 eyes were included, of which 25 eyes received EP TIOL implantation and the remaining 25 received TICL implantation. Preoperative mean ± standard deviation of spherical equivalent (SE) and cylinder was -10.15 ± 4.04 and -2.08 ± 0.86 diopters (D) in the EP TIOL group and -10.21 ± 3.97 and -2.17 ± 0.95 D in the TICL group, respectively. At 2 years of follow-up, there was no significant difference between the mean uncorrected distance visual acuity, corrected distance visual acuity, spherical equivalent, and residual astigmatism between the two groups (P > .05 for all parameters). Ninety-two percent of eyes in the EP TIOL group and 88% of eyes in the TICL group were within ±0.50 D of refractive astigmatism. Vector analysis of astigmatism showed a comparable Correction Index of 0.98 in the EP TIOL group and 0.94 in the TICL group, signifying a mild undercorrection of 2% and 6%, respectively. Two eyes in the TICL group underwent exchange for high vault and one eye required realignment due to significant postoperative rotation. CONCLUSIONS: At least for the first 2 years postoperatively, both toric phakic IOLs were safe and effective in managing high myopic astigmatism with comparable visual results and patient satisfaction. [J Refract Surg. 2021;37(1):7-15.].

Cytochrome P450-mediated estrogen catabolism therapeutic avenues in epilepsy.

Epilepsy is a neuropsychiatric disorder, which does not have any identifiable cause. However, experimental and clinical results have asserted that the sex hormone estrogen level and endocrine system function influence the seizure and epileptic episodes. There are available drugs to control epilepsy, which passes through the metabolism process. Cytochrome P-450 family 1 (CYP1A1) is a heme-containing mono-oxygenase that are induced several folds in most of the tissues and cells contributing to their differential expression, which regulates various metabolic processes upon administration of therapeutics. CYP1A1 gene family has been found to metabolize estrogen, a female sex hormone, which plays a central role in maintaining the health of brain altering the level of estrogen active neuropsychiatric disorder like epilepsy. Hence, in this article, we endeavor to provide an opinion of estrogen, its effects on epilepsy and catamenial epilepsy, their metabolism by CYP1A1 and new way forward to differential diagnosis and clinical management of epilepsy in future.

Refractive surgery with simultaneous collagen cross-linking for borderline corneas - A review of different techniques, their protocols and clinical outcomes.

Simultaneous corneal cross-linking (CXL) has been proposed as an adjunct therapy to corneal refractive procedures to prevent future ectasia, especially when performed in borderline corneas. This review analyses the currently available literature (minimum follow-up 6 months) on corneal refractive surgery and simultaneous CXL (PRK Xtra, LASIK Xtra, and SMILE Xtra) to evaluate the overall results including the safety, efficacy, and potential complications associated with these procedures. A comprehensive literature search of various electronic databases (PubMed, PubMed Central, Cochrane database, and MEDLINE) was performed up to 20th May 2020. Four relevant studies were found for PRK Xtra, 12 for LASIK Xtra, and 3 for SMILE Xtra. The total number of eyes included in this review was 1,512: 294 for PRK Xtra, 221 for PRK-only, 446 eyes for LASIK Xtra, 398 eyes for LASIK-only, 91 for SMILE Xtra and 62 for SMILE-only. Current literature suggests that refractive surgery and simultaneous CXL is generally safe and delivers comparable results in terms of visual and refractive outcomes than refractive surgery alone. However, there is no consensus on a standard cross-linking protocol, and complications such as diffuse lamellar keratitis, central toxic keratopathy, and corneal ectasia following Xtra procedures have been reported. It is therefore suggested that surgeons exercise caution in case-selection and counsel their patients regarding the potential risks and benefits with Xtra procedures. Also, further studies are required to standardize the UV-A irradiation protocols and to evaluate the long-term effect on safety, refractive predictability, and stability of these procedures.

Visual and Refractive Outcomes Following Laser Blended Vision Using Non-linear Aspheric Micro-monovision.

PURPOSE: To report 1-year visual and refractive outcomes following PRESBYOND Laser Blended Vision using non-linear aspheric micro-monovision with the MEL 90 platform (Carl Zeiss Meditec GmbH). METHODS: Data were collected retrospectively for all patients who underwent treatment for simultaneous correction of refractive error and presbyopia from June 2015 to June 2018. Only those patients who completed at least 6 months of follow-up were included in the study. RESULTS: A total of 101 patients with a mean age of 51.05 ± 5.15 years (range: 40 to 65 years), of whom 38 patients had myopic and 63 patients had hyperopic refractive error with or without astigmatism, were included in the study. Mean preoperative spherical equivalent was -3.36 ± 1.86 diopters (D) in the myopia group and +1.75 ± 0.99 D in the hyperopia group. At 1 year, the mean spherical equivalent refraction was +0.13 ± 0.32 D in the distance eye and -1.42 ± 0.33 D (range: -0.88 to -2.50 D) in the near eye in the myopia group and -0.13 ± 0.24 D in the distance eye and -1.28 ± 0.31 D (range: -0.63 to -2.00 D) in the near eye in the hyperopia group. Two eyes in the hyperopia group underwent early enhancement for the near eye at 3 months. Ninety-seven percent of the patients in the myopia group and 96% in the hyperopia group were satisfied with their distance vision. Near vision satisfaction score was 95% for the myopia group and 89% for the hyperopia group. CONCLUSIONS: At 1 year, the aspheric micro-monovision protocol resulted in satisfactory and fairly stable visual outcomes in both myopic and hyperopic individuals. [J Refract Surg. 2020;36(5):300-307.].